Polycomb repressive complex 1 shapes the nucleosome landscape but not accessibility at target genes

Abstract

Polycomb group (PcG) proteins are transcriptional repressors that play important roles in regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin to limit the activity of chromatin remodeling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promoters. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features. To address this important question, we examine the chromatin accessibility and nucleosome landscape at PcG protein-bound promoters in mouse embryonic stem cells using the assay for transposase accessible chromatin (ATAC)-seq. Combined with genetic ablation strategies, we unexpectedly discover that although PcG protein-occupied gene promoters exhibit reduced accessibility, this does not rely on PcG proteins. Instead, the Polycomb repressive complex 1 (PRC1) appears to play a unique role in driving elevated nucleosome occupancy and decreased nucleosomal spacing in Polycomb chromatin domains. Our new genome-scale observations argue, in contrast to the prevailing view, that PcG proteins do not significantly affect chromatin accessibility and highlight an underappreciated complexity in the relationship between chromatin accessibility, the nucleosome landscape, and PcG-mediated transcriptional repression.

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

“…Our observation that chromatin accessibility is independent of transcriptional activity is consistent with studies that failed to detect a causative link between the transcription process and promoter chromatin accessibility at a genome-wide level [54,55]. However, in vitro and modeling studies have proposed that transcription by RNA polymerase II can form complexes which are able to evict nucleosomes and increase chromatin accessibility [31][32][33].…”

Activity of PRC1 and Histone H2AK119 Monoubiquitination: Revising Popular Misconceptions

“…Collectively, these studies demonstrate that cPRC1 subunits are important for chromatin compaction and large‐scale chromatin organization, allowing efficient repression of unwanted genes, and proper patterning and tissue development. That been said, and although Polycomb‐occupied promoters are typically more compact than promoters lacking Polycomb complexes, [ 45 ] the loss of PRC1 or PRC2 in ES cells has minor effect on chromatin accessibility, [ 46 ] suggesting that other mechanisms that restrict promoter accessibility are independent of Polycomb activity.…”

Domain model explains propagation dynamics and stability of K27 and K36 methylation landscapes

“…Intriguingly, PRC2 also methylates its binding partner JARID2 on a K27 mimicking peptide that also can activate the enzyme allosterically (Sanulli et al, 2015). However, other factors including genomic features, bound RNA and H2A ubiquitination by PRC1 are likely to also contribute to K27me3 maintenance (King et al, 2018;Laugesen et al, 2019;Yu et al, 2019). In Drosophila, self-propagation is not sufficient for K27me3 maintenance as sequence elements directing PRC recruitment are also required (Coleman and Struhl, 2017;Laprell et al, 2017).…”