YY1 in hematopoietic stem cells: epigenetic regulation, chromatin architecture, and aging.

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Learn more: PMC Disclaimer | PMC Copyright Notice Curr Opin Hematol . 2026 May 18;33(4):129–136. doi: 10.1097/MOH.0000000000000925 YY1 in hematopoietic stem cells: epigenetic regulation, chromatin architecture, and aging Yinghua Wang a, b, c , Xuan Pan a, b, c Author information Article notes Copyright and License information a Department of Medical Sciences, School of Veterinary Medicine b Carbone Cancer Center c Wisconsin Blood Cancer Research Institute, University of Wisconsin, Madison, Wisconsin, USA ✉ Correspondence to Xuan Pan, VMD, PhD, 515 Easterday Ln., Madison, WI 53706, USA. Tel: +1 608 265 4718; e-mail: xpan24@wisc.edu Issue date 2026 Jul. Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 PMC Copyright notice PMCID: PMC13236036  PMID: 42047481 Abstract Purpose of Review Yin Yang 1 (YY1) is a multifunctional transcription factor (TF) with established roles in lymphocyte development. More recently, its functions as a Polycomb group (PcG) protein and chromatin structural regulator in the hematopoietic system have gained increasing attention. This mini-review summarizes emerging insights into the epigenetic and architectural roles of YY1 in fetal and adult hematopoietic stem cells (HSCs), extending beyond its classical transcriptional activity. We also discuss how altered YY1 function contributes to HSC aging and hematopoietic decline. Recent Findings Recent studies show that YY1 is essential for maintaining HSC quiescence, self-renewal, and engraftment during both fetal and adult hematopoiesis. Mechanistically, YY1 regulates hematopoiesis through PcG-dependent pathways and by shaping higher-order chromatin organization. It mediates long-range chromatin interactions, cooperates with cohesin and CTCF to organize three-dimensional genome architecture, and coordinates transcriptional and metabolic programs critical for stem cell maintenance. Notably, age-associated reductions in YY1 activity are linked to functional impairment of HSCs, implicating YY1 in hematopoietic aging. Summary YY1 acts as a TF, chromatin organizer, and PcG protein in hematopoiesis. Defining its roles in normal and aging HSCs may reveal mechanisms of hematopoietic decline and inform strategies to preserve blood system function. Keywords: chromatin structural regulator, hematopoietic stem cells, Polycomb group, Yin Yang 1 INTRODUCTION Yin Yang 1 (YY1) is a ubiquitously expressed and highly conserved transcription factor (TF) that integrates sequence-specific DNA binding with epigenetic and chromatin-based regulatory functions. YY1 can both activate and repress transcription [ 1 , 2 ], and beyond direct transcriptional regulation, it contributes to higher-order genome organization by mediating long-range DNA interactions between proximal and distal regulatory elements through homodimerization [ 3 – 8 , 9 ▪▪ ]. In addition, YY1 cooperates with Polycomb group (PcG) complexes by recruiting PcG components to chromatin and modulating histone modifications, thereby leading to stable epigenetic repression [ 10 – 13 ]. Consistent with these multifunctional properties, YY1 plays essential roles in early embryonic development, X-chromosome inactivation (XCI), DNA damage repair, hematopoiesis, and hematologic malignancies [ 14 – 18 , 19 ▪ ]. Initially identified through its binding at immunoglobulin loci, YY1 was subsequently shown to be indispensable for both B- and T-lymphocyte development, highlighting its importance in the hematopoietic system [ 16 , 20 – 25 ]. More recently, YY1 has emerged as a critical regulator of hematopoietic stem cell (HSC) biology, where it controls self-renewal, quiescence, and engraftment in both fetal and adult contexts [ 26 ▪▪ , 27 , 28 ]. Although YY1 directly regulates a limited subset of target genes, such as Kit [ 27 ] and the cohesin component SMC3 [ 28 ], genome-wide studies reveal that most transcriptional alterations following YY1 loss occur at loci not directly bound by YY1 [ 26 ▪▪ ], supporting a broader role in shaping chromatin accessibility and epigenomic landscapes. These findings suggest that YY1 functions not only as a classical TF but also as a chromatin architectural regulator, coordinating gene expression programs in hematopoietic stem progenitor cells (HSPCs). In this review, we summarize current understanding of YY1 function in HSCs, with particular emphasis on its roles in PcG-mediated repression and chromatin structural regulation during fetal and adult hematopoiesis. Box 1. Open in a new tab no caption available YIN YANG 1 FUNCTIONS IN HEMATOPOIETIC STEM CELL Genetic and mechanistic studies have established YY1 as an essential regulator of HSC function during both fetal and adult hematopoiesis [ 25 , 26 ▪▪ , 27 , 28 ]. In the adult hematopoietic system, conditional deletion of Yy1 results in severe pancytopenia and a marked reduction in long-term HSC repopulating capacity, whereas ectopic YY1 expression promotes HSC expansion. YY1 deficiency disrupts transcriptional networks governing HSC proliferation, reduces cell surface expression of c-Kit by direct repression of kit gene, impairs stem cell factor/c-Kit signaling, and compromises mechanisms that maintain HSC quiescence [ 27 ]. Beyond its role in adult hematopoiesis, YY1 is also indispensable for fetal hematopoietic development [ 26 ▪▪ ]. During embryogenesis, the fetal liver serves as the primary site of HSC expansion and maturation prior to their migration to the bone marrow (BM) [ 29 , 30 ]. Although the molecular mechanisms underlying the fetal-to-adult hematopoietic transition remain incompletely defined, YY1 has emerged as a critical regulator of this process. Conditional deletion of Yy1 in the fetal hematopoietic system leads to neonatal lethality and profound depletion of the fetal HSC pool. YY1-deficient fetal HSCs display defective migration, fail to engraft in the adult BM niche, and consequently lose their capacity to reconstitute hematopoiesis [ 26 ▪▪ ]. Transcriptomic analyses indicate that Yy1 loss disrupts gene networks involved in cell motility and adhesion in fetal HSPCs. Notably, YY1 does not directly bind to the promoters of most dysregulated genes in fetal HSPCs, suggesting predominantly indirect regulatory mechanisms [ 26 ▪▪ ]. Instead of direct binding at gene loci essential for cell mobility and locomotion, YY1 modulates chromatin accessibility at distal regulatory elements, thereby orchestrating broader epigenetic programs essential for HSPC migration and adhesion [ 26 ▪▪ ]. Collectively, these findings establish YY1 as a critical epigenetic regulator of HSC function across developmental stages and provide a mechanistic framework for understanding how temporally dynamic epigenomic configurations govern the fetal-to-adult transition of hematopoiesis. YIN YANG 1-DEPENDENT POLYCOMB GROUP REGULATION IN HEMATOPOIESIS YY1 is the mammalian orthologue of the Drosophila PcG protein Pleiohomeotic (Pho) and represents one of the few mammalian PcG proteins with intrinsic sequence-specific DNA-binding activity [ 10 ]. In addition to functioning as a conventional TF, YY1 mediates stable gene repression by recruiting PcG complexes to chromatin and promoting deposition of the repressive histone modification H3K27 trimethylation (H3K27me3) [ 10 – 13 ]. In mammals, most PcG proteins function within multiprotein complexes, primarily Polycomb Repressive Complex 1 (PRC1) and PRC2 [ 31 ]. Unlike canonical PRC1 and PRC2 components, YY1 is not a core subunit of these complexes but instead acts upstream to facilitate their recruitment to specific genomic loci [ 10 – 13 ]. A defining feature of YY1-mediated PcG function is the presence of a highly conserved 26–amino acid domain (residues 201–226), termed the REPO (REcruit POlycomb) domain. This domain is necessary and sufficient for recruitment of PcG proteins, including EZH2, to YY1-bound chromatin sites and for local induction of H3K27me3 [ 11 – 13 ]. Although a YY1 mutant lacking the REPO domain (YY1ΔREPO) retains DNA-binding capacity, transcriptional activation potential, transient repression activity, and interactions with coregulators such as HDACs, it is defective in PcG recruitment and PcG-dependent stable repression [ 10 – 12 , 32 ]. These findings established YY1 as a sequence-specific recruiter within the mammalian PcG epigenetic network, helping to resolve the longstanding question of how PcG complexes are targeted to defined genomic regions in the absence of intrinsic DNA-binding activity. PcG proteins play essential roles in HSC biology. Components of PRC1 and PRC2 – including BMI1, CBX7, RING1B, EZH2, EED, and SUZ12 – regulate HSC self-renewal, lineage commitment, and prevention of stem cell exhaustion [ 33 – 40 ]. For example, BMI1 is required for HSC self-renewal [ 33 – 35 ], while EZH2 overexpression preserves HSC potential during serial transplantation [ 36 ]. Consistent with this framework, YY1 and EZH2 exhibit striking functional parallels in hematopoietic development. Conditional deletion of either factor in the B cell lineage results in a developmental blockade at the pro-B stage with impaired distal V-to-DJ rearrangement [ 16 , 41 ], and YY1 co-localizes with EZH2 at the immunoglobulin κ locus [ 42 ]. Importantly, YY1-mediated B cell development is at least partially dependent on its PcG function, as deletion of the REPO domain fails to rescue YY1-null phenotypes and disrupts immunoglobulin (Ig)κ rearrangement [ 42 ]. In contrast to EZH2, which lacks intrinsic DNA-binding activity, YY1 directly binds target DNA sequences and recruits EZH2 to establish local H3K27me3 enrichment [ 11 , 12 ], positioning YY1 as a molecular bridge between sequence recognition and PcG-mediated epigenetic repression. Functional studies in hematopoiesis further demonstrate that YY1-dependent PcG activity is required for stem cell maintenance and balanced lineage output. The YY1 REPO domain is required for Igκ chain rearrangement during B cell development and early T cell survival [ 25 , 42 ]. In addition, the REPO domain is critical for long-term fetal liver HSC self-renewal in vivo [ 26 ▪▪ ]. Retroviral BM transplantation assays reveal that expression of a YY1ΔREPO in YY1-null HSPCs skews hematopoiesis toward myeloid differentiation at the expense of lymphoid development [ 25 ]. These findings indicate that YY1-mediated PcG recruitment is necessary to preserve proper lineage specification, stem cell homeostasis and lymphocyte development. Despite strong evidence supporting YY1 as a PcG recruiter, PcG targeting in mammalian cells is likely multifactorial. YY1 and PcG target genes do not completely overlap across cell types [ 21 , 43 ], and other TFs (e.g., GATA1, RUNX1, REST) and long non-coding RNAs have also been implicated in PcG recruitment [ 44 – 48 ]. Thus, YY1-dependent PcG repression appears to be context- and lineage-specific. YIN YANG 1 AS A CHROMATIN STRUCTURAL REGULATOR IN HEMATOPOIESIS Beyond its role in PcG recruitment, YY1 functions as a chromatin architectural factor that mediates long-range enhancer–promoter interactions and shapes three-dimensional (3D) genome organization. Gene expression frequently depends on physical proximity between distal cis-regulatory enhancers and target promoters, a process achieved through chromatin looping [ 49 – 52 ]. Classical architectural proteins such as CTCF and cohesin organize higher-order chromatin domains and stabilize loop structures [ 53 – 57 ]. More recently, YY1 has emerged as a sequence-specific looping factor capable of directly bridging enhancer and promoter elements through homodimerization, thereby facilitating transcriptional regulation via long-range chromatin interactions [ 3 , 6 – 8 , 9 ▪▪ , 17 , 19 ▪ , 58 ]. Structurally, the C-terminal zinc finger domain of YY1 mediates DNA binding, while the central region (amino acids 201–226, the REPO domain) enables PcG recruitment. Notably, the broader C-terminal portion of YY1 (aa 201–414) is also critical for chromatin looping functions, Ig class switching recombination [ 59 ] and XCI [ 18 ], indicating that YY1 integrates structural and epigenetic regulatory capacities within overlapping domains. Through these properties, YY1 operates not only as a TF but also as a dynamic organizer of chromatin topology. The architectural role of YY1 is particularly evident in B cell development. Conditional deletion of YY1 causes profound defects in B lymphopoiesis, including impaired progression from the pro-B to pre-B stage and reduced mature B cell output [ 7 , 16 , 21 , 42 , 59 – 61 ]. At the immunoglobulin loci, YY1 mediates long-distance DNA interactions required for V (D)J recombination and class-switch recombination (CSR) [ 7 , 16 , 23 , 42 , 59 , 62 ]. YY1 facilitates looping between the intronic Eμ enhancer and the 3΄ regulatory region (3΄RR), thereby promoting antibody diversification [ 59 ]. Mutational analyses demonstrate that a YY1 fragment encompassing amino acids 201–414, which retains DNA binding and the REPO domain but lacks the N-terminal activation domain, is sufficient to restore Eμ–3΄RR looping and rescue CSR [ 59 ]. YY1 also cooperates with cohesin and condensin complexes at the Igκ locus, and co-localizes with EZH2 at multiple regulatory regions, illustrating how chromatin architecture and PcG-dependent repression intersect during lymphoid development [ 42 ]. Genome-wide analyses further support a cooperative relationship between YY1, cohesin, and CTCF in HSPCs. YY1 physically interacts with CTCF and the cohesin component SMC3 through its C-terminal zinc finger domain [ 3 , 17 , 28 , 58 ], and chromatin profiling demonstrates extensive co-occupancy of these factors across the genome. Promoters co-bound by YY1, cohesin, and CTCF are enriched for genes involved in metabolic regulation, whereas cohesin/CTCF-bound loci lacking YY1 are more frequently associated with developmental programs [ 28 ]. These findings suggest that YY1 provides regulatory specificity within cohesin-CTCF-defined chromatin domains, contributing to context-dependent transcriptional outputs during HSC differentiation and metabolism. Consistent with this model, YY1-dependent chromatin organization also contributes to lineage fidelity. Loss of YY1 in pro-B cells disrupts stable B-lineage commitment, enabling altered differentiation into T cell and myeloid lineages. Multi-omic profiling indicates that YY1 deficiency increases chromatin accessibility at alternative lineage genes, suggesting that YY1 maintains lineage identity by constraining chromatin topology and enhancer accessibility [ 63 ▪▪ ]. Mechanistically, YY1-mediated enhancer–promoter contacts are frequently nested within stable CTCF-anchored domains, indicating that YY1 functions within pre-established topological frameworks to confer regulatory precision [ 4 ]. YY1 is required to establish a set of enhancer-promoter loops during G1 cell cycle stage in erythroid cells [ 9 ▪▪ ]. Emerging evidence further suggests that YY1 can promote transcriptional activation through phase-separated condensates that compartmentalize enhancers and coactivators, underscoring its role as a dynamic genome organizer [ 64 ]. Collectively, these findings position YY1 as a multifunctional chromatin organizer in hematopoiesis (Table 1 ). By coordinating enhancer–promoter looping, collaborating with cohesin and CTCF, and intersecting with PcG-mediated repression, YY1 integrates structural genome architecture with epigenetic regulation to maintain HSC identity, enforce lineage commitment, and support lymphoid differentiation (Fig. 1 ). Table 1. YY1 functions as a chromatin architectural regulator YY1 chromatin structural regulation Mechanism Reference Cohesin / CTCF interaction and co-occupancy YY1 physically interacts with CTCF and SMC3 through its C-terminal zinc-finger domain. YY1 co-localizes with SMC3 and CTCF across the genome in HSPCs. [ 4 , 17 , 28 , 58 ] Enhancer–promoter looping YY1 forms homo dimers that facilitate the interaction of active enhancers and proximal promoter elements. YY1 establishes enhancer–promoter loops in erythroid cells during G1-phase entry, highlighting a dynamic, cell-cycle-dependent architectural role. [ 3 , 4 , 6 , 8 , 9 ▪▪ , 19 ▪ ] Long-range chromatin interactions (LRCIs) YY1 cooperates with H3K27ac to mediate LRCIs to promote erythroid differentiation. YY1 orchestrates LRCIs and activation-associated chromatin remodeling across the Th2 cytokine locus [ 8 , 9 ▪▪ , 24 ] Igκ light-chain rearrangement The YY1 PcG domain interacts with condensin and cohesin. YY1 co-localizes with EZH2 and condensin across the Igκ locus to support chromatin organization during recombination. [ 42 ] Ig heavy-chain CSR YY1 mediates long-distance interactions between the intronic Eμ enhancer and the 3΄ regulatory region (3΄RR) during CSR. [ 59 ] XCI YY1 maintains XCI in activated B cells through its C-terminal zinc-finger domain. [ 18 ] PcG-mediated functions in hematopoiesis YY1 PcG/REPO-dependent function is required for balanced lymphoid and myeloid lineage output. The REPO domain is critical for long-term fetal liver HSC self-renewal. [ 25 , 26 ▪▪ ] Transcriptional condensates YY1 forms liquid-liquid phase-separated condensates to compartmentalize coactivators and enhancer elements for gene regulation. [ 64 ] Chromatin accessibility Loss of YY1 in pro-B cells alters chromatin accessibility, repressing B-lineage genes while opening T-cell and myeloid loci, enabling altered differentiation. Deleting YY1 in fetal liver HSPCs alters global chromatin accessibility. [ 26 ▪▪ , 63 ▪▪ ] Open in a new tab * This table is original. FIGURE 1. Open in a new tab YY1 functions as a TF, PcG protein and chromatin structural regulator in hematopoiesis. YY1 can function as a canonical TF that binds directly to the promoters of target genes to regulate transcriptional activation (e.g., Kit or repression (e.g., Smc3 ) in HSPCs. YY1 can also recruit PcG proteins, such as EZH2, via its PcG domain to establish repressive chromatin marks H3K27me3 and stably repress transcription in B cells and HSCs. Furthermore, YY1 contributes to 3D chromatin architecture by forming homodimers and co-localizing with cohesin and CTCF. This complex establishes long-distance enhancer-promoter loops that activate gene transcription, particularly driving metabolic gene expression programs in HSPCs. YIN YANG 1 AND HEMATOPOIETIC STEM CELL AGING YY1 has emerged as a central regulator of aging across multiple tissues, including pancreatic β cells, the nervous system, and skeletal muscle [ 65 ▪ , 66 ▪ , 67 ]. In these settings, YY1 suppresses cellular senescence [ 68 ] and coordinates metabolic programs governing mitochondrial function and stress adaptation [ 69 ▪ , 70 ]. Notably, metabolic interventions such as betaine supplementation can restore YY1-dependent mitochondrial respiration and ameliorate age-associated mitochondrial dysfunction [ 71 ▪ ]. Collectively, these findings position YY1 at the intersection of metabolic regulation and cellular longevity. Metabolic reprogramming is a hallmark of HSC aging [ 72 – 74 ]. Aged HSCs exhibit increased proliferative activity, elevated reactive oxygen species (ROS), impaired mitochondrial function, and altered energy utilization – features closely linked to functional decline [ 72 – 75 , 76 ▪ , 77 , 78 ▪ ]. Concomitantly, the aging hematopoietic system is characterized by expansion of phenotypic HSC numbers, diminished long-term self-renewal capacity, and skewing toward myeloid lineage output [ 79 – 83 ]. The convergence of metabolic dysregulation and HSC dysfunction suggests the involvement of upstream regulators that integrate metabolic homeostasis with HSC functions. Accumulating evidence identifies YY1 as a critical component of this regulatory axis. Genome-wide occupancy analyses demonstrate that genomic regions co-bound by YY1, cohesin, and CTCF are enriched for metabolic gene programs in HSPCs [ 28 ], implicating YY1 function in higher-order chromatin organization of metabolic networks. Consistent with this, loss-of-function studies have shown that YY1 deficiency in HSCs results in hyperproliferation, metabolic rewiring, elevated ROS levels, and compromised mitochondrial function – phenotypes that recapitulate key features of aged HSCs [ 26 ▪▪ , 27 , 28 ]. Moreover, YY1 expression and activity decline with age in murine HSCs [ 84 ▪▪ ], and restoring YY1 expression rescues long-term self-renewal capacity in aged HSCs [ 85 ]. In addition, several key signature genes associated with HSC aging, including Itgb3 , Vwf , and Neo1 [ 86 ], intersect with YY1-dependent regulatory programs [ 87 ▪ , 88 ▪ , 89 ], reinforcing the concept that diminished YY1 activity contributes to age-associated hematopoietic decline. Although age-associated chromatin remodeling in HSCs has been documented [ 90 , 91 ▪▪ ], how aging reshapes higher-order genome architecture and drives functional decline remains unclear. Given YY1's roles as a TF, PcG protein, and structural regulator mediating enhancer–promoter looping, it is well-positioned to link metabolic gene expression with 3D chromatin organization. Future work should clarify how YY1 cooperates with architectural complexes such as cohesin, condensin, and CTCF to maintain chromatin loops and regulatory hubs that support HSC quiescence and metabolism. Key questions include whether age-related YY1 reduction disrupts chromatin topology at metabolic and stemness loci and whether restoring YY1 can rejuvenate chromatin structure and function. Combining single-cell multi-omics, high-resolution chromatin conformation mapping, and functional assays will be critical. Understanding YY1-dependent chromatin architecture may provide a mechanistic framework for HSC aging and reveal strategies to restore youthful hematopoiesis. CONCLUSION As a multifunctional TF, YY1 governs HSC quiescence, self-renewal, and lineage commitment by integrating PcG-mediated repression with high-order chromatin structure. Emerging evidence further identifies YY1 as a key regulator of HSC aging, linking changes in chromatin organization and metabolic homeostasis to progressive stem cell dysfunction. Collectively, these findings position YY1 as a key factor connecting epigenetic regulation, 3D genome architecture, and stem cell longevity and underscore the need to dissect YY1's functions across development and aging to better understand age-associated hematopoietic decline. Acknowledgements This research was supported by NIH grants R03OD026603 and R01HL146540 awarded to X.P. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: ▪ of special interest ▪▪ of outstanding interest REFERENCES 1. Park K, Atchison ML. Isolation of a candidate repressor/activator, NF-E1 (YY-1, d), that binds to the immunoglobulin k 3’ enhancer and the immunoglobulin heavy-chain mE1 site. Proc Natl Acad Sci USA 1991; 88:9804–9808. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Shi Y, Seto E, Chang L-S, et al. Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus E1A protein. Cell 1991; 67:377–388. [ DOI ] [ PubMed ] [ Google Scholar ] 3. Weintraub AS, Li CH, Zamudio AV, et al. YY1 is a structural regulator of enhancer-promoter loops. Cell 2017; 171:1573–1588.e28. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Beagan JA, Duong MT, Titus KR, et al. YY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment. Genome Res 2017; 27:1139–1152. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 5. Figiel M, Szubert F, Luchinat E, et al. Zinc controls operator affinity of human transcription factor YY1 by mediating dimerization via its N-terminal region. Biochim Biophys Acta Gene Regul Mech 2023; 1866:194905. [ DOI ] [ PubMed ] [ Google Scholar ] 6. Liu T, Zhu Q, Kai Y, et al. Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions. Nat Commun 2024; 15:1274. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 7. Phongbunchoo Y, Braikia FZ, Pessoa-Rodrigues C, et al. YY1-mediated enhancer-promoter communication in the immunoglobulin mu locus is regulated by MSL/MOF recruitment. Cell Rep 2024; 43:114456. [ DOI ] [ PubMed ] [ Google Scholar ] 8. Perreault AA, Brown JD, Venters BJ. Erythropoietin regulates transcription and YY1 dynamics in a pre-established chromatin architecture. iScience 2020; 23:101583. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 9▪▪. Lam JC, Aboreden NG, Midla SC, et al. YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle. Nat Genet 2024; 56:1938–1952. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; Acute degradation of YY1 in erythroid cells demonstrates that YY1 is directly required to sustain many enhancer–promoter loops, not compartments or domains. Notably, although YY1 can interact with cohesin, the formation of YY1-dependent enhancer-promoter loops does not involve stalling of cohesin-mediated loop extrusion. Tracking mitosis-to-G1 dynamics identifies a subset of loops that require YY1 for establishment at G1 entry but not for continued maintenance in interphase, highlighting cell-cycle regulation of YY1's chromatin structure function. 10. Atchison L, Ghias A, Wilkinson F, et al. Transcription factor YY1 functions as a PcG protein in vivo. Embo J 2003; 22:1347–1358. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 11. Wilkinson FH, Park K, Atchison ML. Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proc Natl Acad Sci USA 2006; 103:19296–19301. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Srinivasan L, Atchison ML. YY1 DNA binding and PcG recruitment requires CtBP. Genes Dev 2004; 18:2596–2601. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 13. Wilkinson F, Pratt H, Atchison ML. PcG recruitment by the YY1 REPO domain can be mediated by Yaf2. J Cell Biochem 2010; 109:478–486. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 14. Majewski IJ, Ritchie ME, Phipson B, et al. Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells. Blood 2010; 116:731–739. [ DOI ] [ PubMed ] [ Google Scholar ] 15. Castellano G, Torrisi E, Ligresti G, et al. Yin Yang 1 overexpression in diffuse large B-cell lymphoma is associated with B-cell transformation and tumor progression. Cell Cycle 2010; 9:557–563. [ DOI ] [ PubMed ] [ Google Scholar ] 16. Liu H, Schmidt-Supprian M, Shi Y, et al. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev 2007; 21:1179–1189. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 17. Donohoe ME, Zhang LF, Xu N, et al. Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. Mol Cell 2007; 25:43–56. [ DOI ] [ PubMed ] [ Google Scholar ] 18. Syrett CM, Sindhava V, Hodawadekar S, et al. Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells. PLoS Genet 2017; 13:e1007050. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 19▪. Zhu Q, Guo S, Xie J, et al. Distal enhancers regulate mammalian early embryonic lineage differentiation through long-range interactions. Nucleic Acids Res 2026; 54:2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; H3K27ac is concentrated at distal enhancers and coincides with lineage-specific enhancer–promoter loops, supporting that first-lineage decisions are driven by enhancer activity and long-range interactions. YY1, p300, and BRD4 are enriched at the lineage-specific enhancer–promoter loops, driving lineage decisions for morula-to-blastocyst transition. 20. Trabucco SE, Gerstein RM, Zhang H. YY1 regulates the germinal center reaction by inhibiting apoptosis. J Immunol 2016; 197:1699–1707. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 21. Kleiman E, Jia H, Loguercio S, et al. YY1 plays an essential role at all stages of B-cell differentiation. Proc Natl Acad Sci USA 2016; 113:E3911–E3920. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 22. Chen L, Foreman DP, Sant’Angelo DB, et al. Yin Yang 1 promotes thymocyte survival by downregulating p53. J Immunol 2016; 196:2572–2582. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 23. Banerjee A, Sindhava V, Vuyyuru R, et al. YY1 is required for germinal center B cell development. PLoS One 2016; 11:e0155311. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 24. Hwang SS, Kim YU, Lee S, et al. Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation. Proc Natl Acad Sci USA 2013; 110:276–281. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 25. Assumpcao A, Fu G, Singh DK, et al. A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development. Development 2021; 148:dev197319. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 26▪▪. Saka S, Lu Z, Wang Y, et al. Chromatin factor YY1 controls fetal hematopoietic stem cell migration and engraftment in mice. J Clin Invest 2025; 135:e188140. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; YY1 is a key epigenetic regulator of the fetal-to-adult hematopoietic transition. Conditional Yy1 deletion during fetal development causes neonatal lethality and depletion of the fetal HSC pool, and YY1-deficient fetal HSCs show defective migration and fail to engraft the adult BM. Transcriptomic and chromatin analyses indicate that YY1 controls migration/adhesion programs primarily by modulating chromatin accessibility at regulatory elements, rather than by binding promoters of dysregulated genes. 27. Lu Z, Hong CC, Kong G, et al. Polycomb group protein YY1 is an essential regulator of hematopoietic stem cell quiescence. Cell Rep 2018; 22:1545–1559. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Lu Z, Wang Y, Assumpcao A, et al. Yin Yang 1 regulates cohesin complex protein SMC3 in mouse hematopoietic stem cells. Blood Adv 2024; 8:3076–3091. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 29. Ema H, Nakauchi H. Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 2000; 95:2284–2288. [ PubMed ] [ Google Scholar ] 30. Christensen JL, Wright DE, Wagers AJ, et al. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2004; 2:E75. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 31. Chittock EC, Latwiel S, Miller TC, et al. Molecular architecture of polycomb repressive complexes. Biochem Soc Trans 2017; 45:193–205. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 32. Srinivasan L, Pan X, Atchison ML. Transient requirements of YY1 expression for PcG transcriptional repression and phenotypic rescue. J Cell Biochem 2005; 96:689–699. [ DOI ] [ PubMed ] [ Google Scholar ] 33. Iwama A, Oguro H, Negishi M, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the Polycomb gene product Bmi-1. Immunity 2004; 21:843–851. [ DOI ] [ PubMed ] [ Google Scholar ] 34. Park I-k, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423:302–305. [ DOI ] [ PubMed ] [ Google Scholar ] 35. Rizo A, Olthof S, Han L, et al. Repression of BMI1 in normal and leukemic human CD34(+) cells impairs self-renewal and induces apoptosis. Blood 2009; 114:1498–1505. [ DOI ] [ PubMed ] [ Google Scholar ] 36. Kamminga LM, Bystrykh LV, de Boer A, et al. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006; 107:2170–2179. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 37. Lee SC, Miller S, Hyland C, et al. Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis. Blood 2015; 126:167–175. [ DOI ] [ PubMed ] [ Google Scholar ] 38. Xie H, Xu J, Hsu JH, et al. Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell 2014; 14:68–80. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 39. Klauke K, Radulovic V, Broekhuis M, et al. Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation. Nat Cell Biol 2013; 15:353–362. [ DOI ] [ PubMed ] [ Google Scholar ] 40. Cales C, Roman-Trufero M, Pavon L, et al. Inactivation of the polycomb group protein Ring1B unveils an antiproliferative role in hematopoietic cell expansion and cooperation with tumorigenesis associated with Ink4a deletion. Mol Cell Biol 2008; 28:1018–1028. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 41. Su I-h, Basavaraj A, Krutchinsky AN, et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 2003; 4:124–131. [ DOI ] [ PubMed ] [ Google Scholar ] 42. Pan X, Papasani M, Hao Y, et al. YY1 controls Igkappa repertoire and B-cell development, and localizes with condensin on the Igkappa locus. Embo J 2013; 32:1168–1182. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 43. Xi H, Yu Y, Fu Y, et al. Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1. Genome Res 2007; 17:798–806. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 44. Ross J, Mavoungou L, Bresnick EH, et al. GATA-1 utilizes Ikaros and polycomb repressive complex 2 to suppress Hes1 and to promote erythropoiesis. Mol Cell Biol 2012; 32:3624–3638. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 45. Boulay G, Dubuissez M, Van Rechem C, et al. Hypermethylated in cancer 1 (HIC1) recruits polycomb repressive complex 2 (PRC2) to a subset of its target genes through interaction with human polycomb-like (hPCL) proteins. J Biol Chem 2012; 287:10509–10524. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 46. Dietrich N, Lerdrup M, Landt E, et al. REST-mediated recruitment of polycomb repressor complexes in mammalian cells. PLoS Genet 2012; 8:e1002494. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 47. Yu M, Mazor T, Huang H, et al. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell 2012; 45:330–343. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 48. Kaneko S, Li G, Son J, et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev 2010; 24:2615–2620. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 49. Bonev B, Cavalli G. Organization and function of the 3D genome. Nat Rev Genet 2016; 17:772. [ DOI ] [ PubMed ] [ Google Scholar ] 50. de Laat W, Duboule D. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 2013; 502:499–506. [ DOI ] [ PubMed ] [ Google Scholar ] 51. Spitz F. Gene regulation at a distance: from remote enhancers to 3D regulatory ensembles. Semin Cell Dev Biol 2016; 57:57–67. [ DOI ] [ PubMed ] [ Google Scholar ] 52. Levine M, Cattoglio C, Tjian R. Looping back to leap forward: transcription enters a new era. Cell 2014; 157:13–25. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 53. Handoko L, Xu H, Li G, et al. CTCF-mediated functional chromatin interactome in pluripotent cells. Nat Genet 2011; 43:630–638. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 54. Phillips JE, Corces VG. CTCF: master weaver of the genome. Cell 2009; 137:1194–1211. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 55. Sofueva S, Yaffe E, Chan WC, et al. Cohesin-mediated interactions organize chromosomal domain architecture. Embo J 2013; 32:3119–3129. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 56. Hadjur S, Williams LM, Ryan NK, et al. Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature 2009; 460:410–413. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 57. Wutz G, Varnai C, Nagasaka K, et al. Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO J 2017; 36:3573–3599. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 58. Schwalie PC, Ward MC, Cain CE, et al. Co-binding by YY1 identifies the transcriptionally active, highly conserved set of CTCF-bound regions in primate genomes. Genome Biol 2013; 14:R148. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 59. Mehra P, Gerasimova T, Basu A, et al. YY1 controls Emu-3’RR DNA loop formation and immunoglobulin heavy chain class switch recombination. Blood Adv 2016; 1:15–20. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 60. Gerasimova T, Guo C, Ghosh A, et al. A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation. Genes Dev 2015; 29:1683–1695. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 61. Atchison ML. Function of YY1 in long-distance DNA interactions. Front Immunol 2014; 5:45. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 62. Zaprazna K, Atchison ML. YY1 controls immunoglobulin class switch recombination and nuclear activation-induced deaminase levels. Mol Cell Biol 2012; 32:1542–1554. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 63▪▪. Banerjee S, Sanyal S, Hodawadekar S, et al. YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity. Genes Dev 2024; 38:887–914. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; YY1 is essential for B cell lineage commitment at the pro-B stage, as YY1 knockout abolishes B cell fate. YY1-deficient pro-B cells exhibit striking lineage plasticity, generating T cells and other hematopoietic lineages. Multi-omics profiling indicates that YY1 maintains lineage commitment by regulating chromatin-modifying programs and restricting the accessibility of alternative-lineage genes. 64. Wang W, Qiao S, Li G, et al. A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated enhancer clusters. Nucleic Acids Res 2022; 50:4917–4937. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 65▪. Zhang W, Bai L, Xu W, et al. Sirt6 mono-ADP-ribosylates YY1 to promote dystrophin expression for neuromuscular transmission. Adv Sci (Weinh) 2024; 11:e2406390. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; Sirt6 declines in aged muscle and muscle-specific Sirt6 loss reduces dystrophin and accelerates neuromuscular junction dysfunction. Mechanistically, Sirt6 mono-ADP-ribosylates YY1, reducing YY1 occupancy at the dystrophin promoter and delays neuromuscular junction degeneration in aged mice, highlighting YY1 as a modifiable node in neuromuscular aging. 66▪. Yang J, Ma Y, Liu J, et al. Identifying and validating the key regulatory transcription factor YY1 in the aging process of pancreatic beta cells based on bioinformatics. Exp Gerontol 2024; 198:112633. [ DOI ] [ PubMed ] [ Google Scholar ]; Bioinformatics analysis of young vs aged mouse β-cell datasets identifies YY1 as a putative upstream regulator of pancreatic β-cell aging. YY1 expression is reduced in both in vivo and in vitro aging models. Pharmacologic activation with the YY1 agonist eudesmin improves glucose intolerance and β-cell aging markers, and is associated with inhibition of p38/JNK MAPK signaling. 67. Mazor G, Smirnov D, Ben David H, et al. TP73-AS1 is induced by YY1 during TMZ treatment and highly expressed in the aging brain. Aging (Albany NY) 2021; 13:14843–14861. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 68. Wang X, Feng Y, Xu L, et al. YY1 restrained cell senescence through repressing the transcription of p16. Biochim Biophys Acta 2008; 1783:1876–1883. [ DOI ] [ PubMed ] [ Google Scholar ] 69▪. Zhang M, Peng Z, Ping H, et al. Transcription factor Yin-Yang 1 governs cardiac metabolic reprogramming in response to exercise or pathological stress. Am J Physiol Heart Circ Physiol 2025; 329:H899–H906. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; This study demonstrates that YY1 is essential for cardiac metabolic adaptation to both physiological and pathological stress. Conditional Yy1 knockout blunts exercise-induced activation of oxidative/mitochondrial gene networks and suppresses metabolic programs after pressure overload. Mechanistically, YY1 engages p300 and HDAC3 to drive cardiac metabolic reprogramming in response to exercise and pathological stress, respectively. 70. Chen F, Zhou J, Li Y, et al. YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells. EMBO J 2019; 38:e99727. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 71▪. Chen S, He T, Chen J, et al. Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1. J Cachexia Sarcopenia Muscle 2024; 15 5:2104–2117. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; This study shows that dietary betaine improves age-associated muscle loss and mitochondrial dysfunction in old mice through Yy1 , increasing mitochondrial respiration markers and reducing oxidative stress. Aging represses Yy1 in muscle, while betaine restores Yy1 expression and thereby suppresses the mitochondrial regulator Mss51 . YY1 directly represses Mss51 to preserve mitochondrial oxidative capacity and improve energy expenditure. 72. Karimnia N, Harris J, Heazlewood SY, et al. Metabolic regulation of aged hematopoietic stem cells: key players and mechanisms. Exp Hematol 2023; 128:2–9. [ DOI ] [ PubMed ] [ Google Scholar ] 73. Nakamura-Ishizu A, Ito K, Suda T. Hematopoietic stem cell metabolism during development and aging. Dev Cell 2020; 54:239–255. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 74. Mohrin M, Shin J, Liu Y, et al. Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science 2015; 347:1374–1377. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 75. Ito K, Hirao A, Arai F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 2006; 12:446–451. [ DOI ] [ PubMed ] [ Google Scholar ] 76▪. Lalioti ME, Romero-Mulero MC, Karabacz N, et al. Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells. Nat Cell Biol 2025; 27:1367–1380. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; This study presents an integrated metabolome, lipidome, and transcriptome of low-input human CD34 + CD38 + HSPCs across differentiation, aging, and acute myeloid leukemia, providing a high-resolution resource for linking metabolism to stem cell state. A key finding is that choline is enriched in HSPCs relative to progenitors but declines with aging and is further reduced in acute myeloid leukemia. Functionally, choline supplementation boosts lipid production and enhances HSPC functions. 77. Ho TT, Warr MR, Adelman ER, et al. Autophagy maintains the metabolism and function of young and old stem cells. Nature 2017; 543:205–210. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 78▪. Su TY, Hauenstein J, Somuncular E, et al. Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets. Nat Commun 2024; 15:7966. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; This study dissects hematopoietic aging across distinct HSC subsets stratified by CD49b, linking HSC heterogeneity to age-associated functional decline. Both lymphoid-biased and myeloid-biased HSC subsets progressively shift toward increased myeloid output with age. In parallel, subset-specific gene expression and regulatory programs change in a progressive manner that begins as early as the juvenile stage, supporting an intrinsic, stepwise remodeling of HSC state during aging. 79. de Haan G, Lazare SS. Aging of hematopoietic stem cells. Blood 2018; 131:479–487. [ DOI ] [ PubMed ] [ Google Scholar ] 80. Beerman I, Bhattacharya D, Zandi S, et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci USA 2010; 107:5465–5470. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 81. Cho RH, Sieburg HB, Muller-Sieburg CE. A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 2008; 111:5553–5561. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 82. Dykstra B, Olthof S, Schreuder J, et al. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med 2011; 208:2691–2703. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 83. Sudo K, Ema H, Morita Y, et al. Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 2000; 192:1273–1280. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 84▪▪. Liu X, Zhang C, Lv J, et al. Pyrroloquinoline quinone reprograms the single-cell landscape of immune aging in hematopoietic immune system. Aging Cell 2025; 24:e70050. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; Hematopoietic system aging is accompanied by broad increases in inflammation and oxidative-stress programs across immune cell populations. Notably, YY1 expression declines in aged HSCs, and pyrroloquinoline quinone treatment increases YY1 expression and improves aging-related defects in HSPC self-renewal and differentiation potential. 85. Ma S, Wang S, Ye Y, et al. Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues. Cell Stem Cell 2022; 29:990–1005.e10. [ DOI ] [ PubMed ] [ Google Scholar ] 86. Flohr Svendsen A, Yang D, Kim K, et al. A comprehensive transcriptome signature of murine hematopoietic stem cell aging. Blood 2021; 138:439–451. [ DOI ] [ PubMed ] [ Google Scholar ] 87▪. Yang F, Wang M. Yin Yang 1 protein-activated N-acetyltransferase 10 drives cell malignant progression of osteosarcoma through ac4C acetylation of integrin beta3. J Bone Oncol 2025; 53:100701. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; YY1 transcriptionally activates NAT10, which in turn increases ITGB3 expression in osteosarcoma. Genetic perturbation shows that YY1 or NAT10 depletion suppresses proliferation/migration/invasion and enhances apoptosis, while ITGB3 overexpression rescues NAT10-knockdown phenotypes. 88▪. Gao Y, Hu Y, Zhu Y, et al. Pan-cancer analysis reveals netrin-1 receptors as potential tumor biomarkers and immune-related therapeutic targets. Sci Rep 2025; 15:44015. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; Pan-cancer analysis across 33 solid tumors suggests cancer-type–dependent roles for NTN1 and its receptor NEO1, with context-specific associations consistent with either oncogenic or tumor-suppressive behavior. The study implicates YY1 (with HDAC1/2) as a candidate regulator for NEO1 expression. 89. Tao Q, Lu Y, Qi Y, et al. Hypoxia promotes the expression of Von Willebrand factor in breast cancer cells by up-regulating the transcription factor YY1 and down-regulating the hsa-miR-424. Eur J Pharmacol 2022; 934:175308. [ DOI ] [ PubMed ] [ Google Scholar ] 90. Tang B, Wang X, He H, et al. Aging-disturbed FUS phase transition impairs hematopoietic stem cells by altering chromatin structure. Blood 2024; 143:124–138. [ DOI ] [ PubMed ] [ Google Scholar ] 91▪▪. Hu Y, Horlbeck MA, Zhang R, et al. Multiscale footprints reveal the organization of cis-regulatory elements. Nature 2025; 638:779–786. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]; This study introduces PRINT/seq2PRINT, a multiscale footprinting and deep-learning framework that infers transcription factor and nucleosome occupancy from bulk and single-cell chromatin accessibility data, enabling genome-wide analysis of cis-regulatory element (CRE) architecture. In aged murine HSCs, the authors identify age-associated remodeling of CRE structure, including reduced nucleosome footprints and altered motif composition. Notably, the approach predicts reduced YY1 activity at aged HSC cis-regulatory elements and implicates YY1 as a contributor to nucleosome positioning across cell types. Articles from Current Opinion in Hematology are provided here courtesy of Wolters Kluwer Health ACTIONS View on publisher site PDF (571.1 KB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

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