Inseparable RNA binding and chromatin modification activities of a nucleosome-interacting surface in EZH2.

Polycomb repressive complex 2 (PRC2) interacts with RNA in cells, but there is no consensus on how RNA regulates PRC2 canonical functions, including chromatin modification and the maintenance of transcription programs in lineage-committed cells. We assayed two separation-of-function mutants of the PRC2 catalytic subunit EZH2, defective in RNA binding but functional in methyltransferase activity. We find that part of the RNA-binding surface of EZH2 is required for chromatin modification, yet this activity is independent of RNA.

The apparent loss of PRC2 chromatin occupancy as an artifact of RNA depletion.

RNA has been implicated in the recruitment of chromatin modifiers, and previous studies have provided evidence in favor and against this idea. RNase treatment of chromatin is commonly used to study RNA-mediated regulation of chromatin modifiers, but the limitations of this approach remain unclear. RNase A treatment during chromatin immunoprecipitation (ChIP) reduces chromatin occupancy of the H3K27me3 methyltransferase Polycomb repressive complex 2 (PRC2).

PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1.

Polycomb repressive complex 2 (PRC2) mediates H3K27me3 deposition, which is thought to recruit canonical PRC1 (cPRC1) via chromodomain-containing CBX proteins to promote stable repression of developmental genes. PRC2 forms two major subcomplexes, PRC2.1 and PRC2.

Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells.

Driver mutations in genes encoding histone H3 proteins resulting in p.Lys27Met substitutions (H3-K27M) are frequent in pediatric midline brain tumors. However, the precise mechanisms by which H3-K27M causes tumor initiation remain unclear.

If You Like It Then You Shoulda Put Two "RINGs" on It: Delineating the Roles of vPRC1 and cPRC1.

To delineate the roles of variant (vPRC1) and canonical (cPRC1) Polycomb repressive complex 1, Blackledge et al. (2020) and Tamburri et al. (2020) elegantly disrupt RING1A/B catalytic activity without affecting stability of either complex and then explore the precise contribution of vPRC1-mediated H2AK119ub1 to Polycomb-mediated gene repression.

PRC2.1 and PRC2.2 Synergize to Coordinate H3K27 Trimethylation.

Polycomb repressive complex 2 (PRC2) is composed of EED, SUZ12, and EZH1/2 and mediates mono-, di-, and trimethylation of histone H3 at lysine 27. At least two independent subcomplexes exist, defined by their specific accessory proteins: PRC2.1 (PCL1-3, EPOP, and PALI1/2) and PRC2.

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.

The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.

PRC2 mediated H3K27 methylations in cellular identity and cancer.

The Polycomb Repressive Complex 2 (PRC2) is a multiprotein chromatin modifying complex that is essential for vertebrate development and differentiation. It is composed of a trimeric core of SUZ12, EED and EZH1/2 and is responsible for catalysing both di-methylation and tri-methylation of Histone H3 at lysine 27 (H3K27me2/3). Both H3K27 methylations contribute to the role of PRC2 in maintaining cellular identity.

A chromatin-independent role of Polycomb-like 1 to stabilize p53 and promote cellular quiescence.

Polycomb-like proteins 1-3 (PCL1-3) are substoichiometric components of the Polycomb-repressive complex 2 (PRC2) that are essential for association of the complex with chromatin. However, it remains unclear why three proteins with such apparent functional redundancy exist in mammals. Here we characterize their divergent roles in both positively and negatively regulating cellular proliferation.

MutSβ and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells.

Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington's disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA repair complex MutSβ (MSH2-MSH3 heterodimer) is required in mice for on-going expansions of long, disease-causing alleles.