Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put

By J. Simon, Robert E. Kingston. Molecules and Cells, 2013

713 citations recorded by the source corpus.

Summary Polycomb repressive complexes are conserved chromatin regulators with key roles in multicellular development, stem cell biology, and cancer. New findings advance molecular understanding of how they target to sites of action, interact with and alter local chromatin to silence genes, and maintain silencing in successive generations of proliferating cells. Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence many key developmental regulators and are centrally integrated in the transcriptional circuitry of embryonic and adult stem cells. PRC2 trimethylates histone H3 on lysine-27 (H3-K27me3) and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs and these signature activities are deployed to select and silence genomic targets is the subject of intense current investigation. We review recent advances on targeting, modulation, and functions of PRC1 and PRC2, and we consider progress on defining transcriptional steps impacted in Polycomb silencing. Key recent findings demonstrate PRC1 targeting independent of H3-K27me3 and emphasize nonenzymatic PRC1-mediated compaction. We also evaluate expanding connections between Polycomb machinery and non-coding RNAs. Exciting new studies supply the first systematic analyses of what happens to Polycomb complexes, and associated histone modifications, during the wholesale chromatin reorganizations that accompany DNA replication and mitosis. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell cycle progression.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/82937e0fe08097a6dc2e672f5e508bf922861891

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In Molecular Biology

Citations in the corpus

Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation (2014, background): “Previous studies report that specific polycomb target sites rely on transcription factors or long noncoding RNAs (lncRNAs) for normal polycomb protein recruitment (Simon and Kingston, 2013).”
Epigenetic plasticity and the hallmarks of cancer (2017, background): “Context-specific repression of lineage-specific developmental genes is enforced by Polycomb repressors, such as the histone H3 Lys(27) (H3K27) methyltransferase EZH2 (enhancer of zeste homolog 2) (6, 16).”
The physics of epigenetics (2015, background): “…binding for nucleosome arrays with long but not with short DNA linkers, pointing to a facilitated spreading of HP1 on long NRL substrates. b. Polycomb-mediated heterochromatin Polycombs are family proteins that mediate transcriptional silencing (Di Croce and Helin, 2013; Simon and Kingston, 2013).”
Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. (2013, background): “…the identification of specific loci with gain of H3K27me3 in the context of overall reduction of this epigenetic mark (in K27Mmutant tumors) raises interesting questions about the molecular mechanisms behind PRC2 targeting, which is still a field of intense research (Simon and Kingston, 2013).”