Polycomb group (PcG) proteins are an important group of transcriptional repressors that act by modifying chromatin. PcG target genes are covered by the repressive chromatin mark H3K27me3. Polycomb repressive complex 2 (PRC2) is a multiprotein complex that is responsible for generating H3K27me3. In , PRC2 is recruited by Polycomb Response Elements (PREs) and then trimethylates flanking nucleosomes, spreading the H3K27me3 mark over large regions of the genome, the "Polycomb domains." What defines the boundary of a Polycomb domain? There is experimental evidence that insulators, PolII, and active transcription can all form the boundaries of Polycomb domains. Here we divide the boundaries of larval Polycomb domains into six different categories. In one category, genes are transcribed toward the Polycomb domain, where active transcription is thought to stop the spreading of H3K27me3. In agreement with this, we show that introducing a transcriptional terminator into such a transcription unit causes an extension of the Polycomb domain. Additional data suggest that active transcription of a boundary gene may restrict the range of enhancer activity of a Polycomb-regulated gene.
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http://dx.doi.org/10.1534/genetics.120.303642 | DOI Listing |
Nat Struct Mol Biol
January 2025
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin compacted by gene-repressing factors are unknown.
View Article and Find Full Text PDFJCI Insight
December 2024
Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Enhancer of Zeste Homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and genes repression. EZH2 is overexpressed in many cancers and studies in mice attributed both pro-oncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in PDAC patients is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression.
View Article and Find Full Text PDFMol Cell
December 2024
Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK; Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK. Electronic address:
Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one of the two marks. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here, we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, thereby promoting a poised state.
View Article and Find Full Text PDFJ Med Virol
December 2024
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA.
Mol Plant
January 2025
College of Life Sciences, Beijing Normal University, Beijing, 100875, China; National Institute of Biological Sciences, Beijing 102206, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 10084, China. Electronic address:
Trimethylation of histone H3K4 (H3K4me3) is widely distributed at numerous actively transcribed protein-coding genes throughout the genome. However, the interplay between H3K4me3 and other chromatin modifications in plants remains poorly understood. In this study, we show that the Arabidopsis thaliana ALFIN-LIKE (AL) proteins contain a C-terminal PHD finger capable of binding to H3K4me3 and a PHD-associated AL (PAL) domain that interacts with components of the Polycomb repressive complex 1, thereby facilitating H2A ubiquitination (H2Aub) at H3K4me3-enriched genes throughout the genome.
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