Ubiquitylated H2A.Z is associated with diverse types of silenced chromatin including methylated CpG islands and homopurine/homopyrimidine sequences

Ubiquitylated H2A.Z is associated with diverse types of silenced chromatin including methylated CpG islands and homopurine/homopyrimidine sequences | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Ubiquitylated H2A.Z is associated with diverse types of silenced chromatin including methylated CpG islands and homopurine/homopyrimidine sequences Bakhtiyar Taghizada , Marlee K. Ng , View ORCID Profile Ulrich Braunschweig , Benjamin J. Blencowe , Peter Cheung doi: https://doi.org/10.1101/759852 Bakhtiyar Taghizada 1 Department of Biology, York University , Toronto, ON, M3J 1P3, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marlee K. Ng 1 Department of Biology, York University , Toronto, ON, M3J 1P3, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ulrich Braunschweig 2 Donnelly Centre, University of Toronto , Toronto, ON, M5S 3E1, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ulrich Braunschweig Benjamin J. Blencowe 2 Donnelly Centre, University of Toronto , Toronto, ON, M5S 3E1, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Peter Cheung 1 Department of Biology, York University , Toronto, ON, M3J 1P3, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: pmcheung{at}yorku.ca Abstract Full Text Info/History Metrics Preview PDF ABSTRACT H2A.Z monoubiquitylation has been linked to transcriptional repression, but the molecular details involved remain unclear. To address this, we developed a unique ubiquitylation-dependent auto-biotinylation approach, named H2A.Z-UAB, to purify ubiquitylated H2A.Z (H2A.Zub) mononucleosomes for biochemical and genome-wide analyses. We found that H2A.Zub nucleosomes are enriched for the repressive histone post-translational modification H3K27me3 but depleted of H3K4 methylation and other active transcription-associated modifications. ChIP-seq analyses revealed that H2A.Zub-nucleosomes associate with repressive chromatin states and are mostly enriched at genes with low or no expression. Consistent with the biochemical analyses, H2A.Zub ChIP-seq peaks align with regions depleted of H3K4 methylation, H3K27 acetylation, but enriched for H3K27me3. We further observed a strong correlation between high levels of H2A.Zub and DNA methylation, particularly at methylated CpG-rich islands. Finally, we found that a significant proportion of H2A.Zub peaks correspond to homopurine/homopyrimidine sequences that are generally linked to silenced genes and repressive chromatin. Collectively, these findings suggest that H2A.Z ubiquitylation plays an overarching role in global transcriptional silencing through its association with multiple types of repressive mechanisms. Download figure Open in new tab Competing Interest Statement The authors have declared no competing interest. Footnotes This version contains new and more extensive bioinformatics analyses. The general conclusion linking H2A.Z ubiquitylation to gene silencing in the original manuscript remains the same, but the new version contains more in-depth and new findings as well as new validation/follow up experiments. We have also removed the biochemical interaction data in the original manuscript as that would fit better as a separate and independent study. Funder Information Declared Canadian Cancer Society, https://ror.org/017343w90 , 704315 Canadian Institutes of Health Research, https://ror.org/01gavpb45 , MOP-136902 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted April 10, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Blencowe , Peter Cheung bioRxiv 759852; doi: https://doi.org/10.1101/759852 Share This Article: Copy Citation Tools Ubiquitylated H2A.Z is associated with diverse types of silenced chromatin including methylated CpG islands and homopurine/homopyrimidine sequences Bakhtiyar Taghizada , Marlee K. Ng , Ulrich Braunschweig , Benjamin J. 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