What does the PRC2 complex do?
PRC2 also contributes to chromatin compaction, and catalyses the methylation of histone H3 at lysine 27. PRC2 is involved in various biological processes, including differentiation, maintaining cell identity and proliferation, and stem-cell plasticity.
Is PRC2 a methyltransferase?
PRC2 is a methyltransferase with activity toward lysine 27 on histone H3 (H3K27). The SET-domain-containing component (EZH1 or EZH2) is closely associated with several other subunits.
How does PRC2 work?
Polycomb repressive complex 2 (PRC2) is a chromatin-modifying enzyme that catalyses the methylation of histone H3 at lysine 27 (H3K27me1/2/3). This complex maintains gene transcriptional repression and plays an essential role in the maintenance of cellular identity as well as normal organismal development.
Does PRC2 activate transcription?
This leads to a dilution of PRC2 concentration at promoters, reduces H3K27me3 methylation at promoters and may subsequently lead to transcriptional activation [45,52,53]. These data suggest that PRC2 has the ability to sense, whether directly or indirectly, the DNA methylation status of target sites.
What is PRC1 and PRC2?
The Polycomb repressive complexes PRC1 and PRC2 act non-redundantly at target genes to maintain transcriptional programs and ensure cellular identity. PRC2 methylates lysine 27 on histone H3 (H3K27me), while PRC1 mono-ubiquitinates histone H2A at lysine 119 (H2Aub1).
Where is PRC2 located?
The PRC2 complex appears to be present at sites of DNA double-strand breaks where it promotes repair of such breaks by non-homologous end joining. The PRC2 is evolutionarily conserved, and has been found in mammals, insects, fungi, and plants.
Does PRC2 bind to H3K27me3?
PRC2 methylates histone lysine residues, mainly on H3K27 (2, 5–7), and also binds to the H3K27me3 mark (32). Efficient binding requires a ternary complex of EZH2, EED, and SUZ12 but is independent of the catalytic SET domain of EZH2 (32).
What is an EZH2 inhibitor?
EZH2 inhibits genes responsible for suppressing tumor development, and blocking EZH2 activity may slow tumor growth. EZH2 has been targeted for inhibition because it is upregulated in multiple cancers including, but not limited to, breast, prostate, melanoma, and bladder cancer.
How is DNA methylated?
DNA methylation is an epigenetic mechanism used by cells to control gene expression. DNA methylation refers to the addition of a methyl (CH3) group to the DNA strand itself, often to the fifth carbon atom of a cytosine ring.
What is epigenetic expression?
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.
What does acetylation of histones do?
Acetylation of histones alters accessibility of chromatin and allows DNA binding proteins to interact with exposed sites to activate gene transcription and downstream cellular functions.
What does H3 in H3K27me3 signify?
H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein. This tri-methylation is associated with the downregulation of nearby genes via the formation of heterochromatic regions.
What are the subunits of the PRC2 complex?
In mammals, the PRC2 core complex consists of EED, SUZ12, NURF55, Rbap46/48, and the catalytic subunits EZH1 or EZH2.
What is the function of polycomb repressive complex PRC2?
In mammals, two main Polycomb group complexes exist — Polycomb repressive complex 1 (PRC1) and 2 (PRC2). PRC1 compacts chromatin and catalyses the monoubiquitylation of histone H2A. PRC2 also contributes to chromatin compaction, and catalyses the methylation of histone H3 at lysine 27.
How does the PCL protein interact with PRC2?
PCL proteins interact with PRC2 through EZH2, and to some extent through SUZ12 and the histone chaperones RbAp46 and RbAp48 (ref. 20 ). Genome-wide studies showed that PCL2 co-occupied PRC2 target genes 21, 22.
Are there any copies of PRC2 in mammals?
Notably, the PRC2 components, in contrast to those of PRC1, underwent little duplication in mammals, with vertebrates containing two copies of enhancer of zeste homologue, EZH1 and EZH2 (ref. 12 ). Drosophila has two copies of the EED homologue, ESC and ESCL.