Abstract
Polycomb repressive complex 2 (PRC2) is a multisubunit protein complex essential for the development of multicellular organisms. Recruitment of PRC2 to target genes, followed by deposition and propagation of its catalytic product histone H3 lysine 27 trimethylation (H3K27me3), are key to the spatiotemporal control of developmental gene expression. Recent breakthrough studies have uncovered unexpected roles for substoichiometric PRC2 subunits in these processes. Here, we elaborate on how the facultative PRC2 subunits regulate catalytic activity, locus-specific PRC2 binding, and propagation of H3K27me3, and how this affects chromatin structure, gene expression, and cell fate.
Highlights
Polycomb repressive complex 2 (PRC2) comprises the core subunits EZH1/2, EED, SUZ12, and RBBP4/7 together with a wide range of substoichiometric subunits [5,6,7]
These experiments convincingly showed that the core of PRC2 is associated with a number of subunits that are present at substoichiometric levels, including PHF1, MTF2, PHF19 ( referred to as Polycomblike (PCL) 1, -2 and -3; homologs of Drosophila PCL), PRC2-associated LCOR isoform 1 (PALI1), EPOP, JARID2, and AEBP2 [23,24,25]
We mainly focus on PRC2 in mouse embryonic stem cells, as these have yielded key insights into Polycomb regulation
Summary
In the search for proteins that modulate PRC2 function, various groups have taken an unbiased approach by performing PRC2 affinity purification coupled to tandem mass spectrometry (AP-MS) (Figure 1) These experiments convincingly showed that the core of PRC2 is associated with a number of subunits that are present at substoichiometric levels, including PHF1, MTF2, PHF19 ( referred to as Polycomblike (PCL) 1, -2 and -3; homologs of Drosophila PCL), PALI1 ( referred to as C10ORF12), EPOP ( known as C17ORF96), JARID2, and AEBP2 [23,24,25]. The recruitment of the H3K36me demethylase NO66 by PHF19 could facilitate the removal of H3K36me and deposition of H3K27me during differentiation [45] This provides a potential mechanism linking changes in cellular state and potency to H3K27 methylation, but whether PCL proteins are important for differentiation to distinct cell types is unknown.
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