Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms

Abstract

Polycomb group (PcG) proteins function as vital epigenetic regulators in various biological processes, including pluripotency, development, and carcinogenesis. PcG proteins form multicomponent complexes, and two major types of protein complexes have been identified in mammals to date, Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The PRC1 complexes are composed in a hierarchical manner in which the catalytic core, RING1A/B, exclusively interacts with one of six Polycomb group RING finger (PCGF) proteins. This association with specific PCGF proteins allows for PRC1 to be subdivided into six distinct groups, each with their own unique modes of action arising from the distinct set of associated proteins. Historically, PRC1 was considered to be a transcription repressor that deposited monoubiquitylation of histone H2A at lysine 119 (H2AK119ub1) and compacted local chromatin. More recently, there is increasing evidence that demonstrates the transcription activation role of PRC1. Moreover, studies on the higher-order chromatin structure have revealed a new function for PRC1 in mediating long-range interactions. This provides a different perspective regarding both the transcription activation and repression characteristics of PRC1. This review summarizes new advancements regarding the composition of mammalian PRC1 and accompanying explanations of how diverse PRC1-associated proteins participate in distinct transcription regulation mechanisms.

Epigenetic regulation of retinal development

“…Of those, the evolutionarily conserved Polycomb (PcG) and Trithorax (TrxG) were first discovered in Drosophila melanogaster as master regulators of Hox gene expression and found to play important roles in embryonic stem (ES) cell self-renewal, cell fate choice, proliferation, apoptosis, cell cycle regulation, plasticity and regeneration [ 29 – 31 ]. PcG forms at least two main repressive complexes: Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2 (PRC2) [ 32 , 33 ]. Methylation of lysine 27 on histone H3 (H3K27me) is catalyzed by the activity of PRC2; as a consequence, PRC1 is recruited, and this leads to a cascade of gene-silencing events [ 34 , 35 ].…”

TBX2 controls a proproliferative gene expression program in melanoma

“…Gene ontology analysis of the mass spectrometry results obtained using a false discovery rate of 1% (Fig. 6A) revealed interaction of Tbx2 with factors implicated in gene regulation and nuclear functions, most notably including the BCOR/polycomb repressive complex 1.1 (PRC1.1) complex (P = 9.132 × 10 −7 ) comprising BCOR, BCORL1, KDM2B, PCGF1, and SKP1, which can play both positive and negative regulatory roles in gene expression (Gil and O'Loghlen 2014;Cohen et al 2019;Geng and Gao 2020). In addition to multiple components of the BCOR complex, other cofactors identified include the nuclear receptor corepressor 1 (NCOR1) and NCOR2 complexes (Mottis et al 2013) and CHD7, a helicase implicated in chromatin remodeling (Bouazoune and Kingston 2012).…”

Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome

“…two main Polycomb complexes are PRC1 and PRC2 (reviewed in Barbour et al, 2020;Cohen et al, 2020;Geng and Gao, 2020). The PRC1 complex acts as an E3 ubiquitin ligase that monoubiquitinates lysine 119 of histone H2A (H2AK119ub1) (De Napoles et al, 2004;Wang et al, 2004).…”