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Review
. 2020 Nov 14;21(22):8594.
doi: 10.3390/ijms21228594.

Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms

Affiliations
Review

Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms

Zhuangzhuang Geng et al. Int J Mol Sci. .

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.

Keywords: PRC1; chromatin structure; transcription regulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The domain architecture of Polycomb group RING finger (PCGF) proteins and the composition of Polycomb Repressive Complex 1 (PRC1) complexes. (a) PCGF proteins share highly conserved protein domains (RING and RING finger and WD40-associated ubiquitin-like (RAWUL)) and unique protein domains (PS) are only present in PCGF2/4; (b) The classification of PRC1 complexes. Based on PCGF proteins, PRC1 can be divided into six categories, PRC1.1–6. In the presence of RING1 and YY1 Binding Protein (RYBP)/YY1 Associated Factor 2 (YAF2) or CBX/PHC/SCM proteins, PRC1 can be classified as canonical PRC1 complexes (cPRC1) and non-canonical PRC1 complexes (ncPRC1). Inserts on the left bottom show the corresponding Drosophila complexes.
Figure 2
Figure 2
PRC1-mediated transcription repression. (a) Crosstalk between cPRC1 and PRC2. PRC2 deposits tri-methylation of histone H3 at lysine 27 (H3K27me3) to genomic loci. Then, CBX proteins drive cPRC1 to PRC2 pre-occupied loci and deposit monoubiquitylation of histone H2A at lysine 119 H2AK119ub1; (b) Crosstalk between ncPRC1 and PRC2. ncPRC1 approaches the genomic loci first and catalyzes H2AK119ub1; PRC2 recognizes and occupies the same region through JARID; (c) cPRC1 complexes mediate chromatin compaction to repress target genes, which is mediated by the interaction between positively charged region of CBX proteins and nucleosomes, and the self-polymerization of PHC proteins.
Figure 3
Figure 3
PRC1-mediated transcription activation. (a) Some PRC1-associated proteins directly or indirectly neutralize the H2AK119ub1 enzymatic activity of PRC1; (b) AUTS2-containing PRC1.3/5 is recruited by transcription factors and sequentially drives P300 to the same loci for acetylation of histone H3 at lysine 27 (H3K27ac).
Figure 4
Figure 4
PRC1-mediated looping formation. (a) PRC1-mediated looping formation depends on the polymerization of PHC proteins’ sterile alpha motif (SAM) domain. It is unclear if ncPRC1 also is involved in long-range chromatin architecture regulation; (b) PRC1-mediated loops work in two patterns to repress anchored genes, either by chromatin compaction or co-occupied two promoters; (c) PRC1-mediated loop establishes contact between the promoter and active enhancer to activate anchored gene expression.

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