The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo

The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo María Lorena Martínez Quiles , View ORCID Profile Barbara H Jennings doi: https://doi.org/10.1101/2022.09.17.508372 María Lorena Martínez Quiles Department of Biological and Medical Sciences, Oxford Brookes University , Oxford, OX3 0BP, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Barbara H Jennings Department of Biological and Medical Sciences, Oxford Brookes University , Oxford, OX3 0BP, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Barbara H Jennings For correspondence: bjennings{at}brookes.ac.uk Abstract Full Text Info/History Metrics Preview PDF ABSTRACT Promoter-proximal pausing of RNA polymerase II (RNAP II) at the early elongation checkpoint is a key regulatory step in developmental and stimulus-responsive gene expression. How pausing is established and modulated in a gene-specific manner during animal development remains unclear. The Groucho (Gro)/Transducin-like Enhancer of split (TLE) family of co-repressors is widely used by transcription factors to repress transcription, yet the mechanism of Gro-mediated repression in vivo is unresolved. Here, we combine genome-wide chromatin profiling with in vivo genetic analysis in Drosophila melanogaster to test whether Gro regulates RNAP II pausing. Analysis of ChIP-seq data across distinct cell types shows that Gro recruitment is largely cell-type specific but consistently occurs as discrete peaks within accessible, enhancer-associated chromatin. Gro occupancy frequently overlaps promoters enriched for pausing regulators, including Negative Elongation Factor (NELF), GAGA Factor (GAF), and components of Positive Transcription Elongation Factor b (P-TEFb), without excluding their recruitment. Using a sensitised wing-specific knockdown assay, we demonstrate that partial depletion of NELF subunits, GAF, and 7SK snRNP components synergistically enhances gro phenotypes beyond additive effects. These genetic interactions support a shared role in regulating transcription during development. Our findings support a model in which Gro attenuates transcription by modulating progression through the P-TEFb-dependent early elongation checkpoint in vivo. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been revised with updates to the text, figures and analysis, and the scope of the study has been refined prior to journal submission. Funder Information Declared Oxford Brookes University - Nigel Groome Studentship Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted March 16, 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. You are going to email the following The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo María Lorena Martínez Quiles , Barbara H Jennings bioRxiv 2022.09.17.508372; doi: https://doi.org/10.1101/2022.09.17.508372 Share This Article: Copy Citation Tools The co-repressor Groucho limits progression through the early transcription elongation checkpoint in vivo María Lorena Martínez Quiles , Barbara H Jennings bioRxiv 2022.09.17.508372; doi: https://doi.org/10.1101/2022.09.17.508372 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Developmental Biology Subject Areas All Articles Animal Behavior and Cognition (7995) Biochemistry (18704) Bioengineering (14815) Bioinformatics (44306) Biophysics (22537) Cancer Biology (19659) Cell Biology (26828) Clinical Trials (138) Developmental Biology (13922) Ecology (20948) Epidemiology (2067) Evolutionary Biology (25404) Genetics (16137) Genomics (23451) Immunology (18656) Microbiology (42369) Molecular Biology (18014) Neuroscience (93230) Paleontology (696) Pathology (2975) Pharmacology and Toxicology (5079) Physiology (8090) Plant Biology (15961) Scientific Communication and Education (2094) Synthetic Biology (4546) Systems Biology (10212) Zoology (2381)

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