EZH2
This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene.
Full Name
Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit
Research Area
Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0> H3K27me1> H3K27me2 (PubMed:22323599, PubMed:30923826).
Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.
Biological Process
B cell differentiation Source: Ensembl
Cardiac muscle hypertrophy in response to stress Source: Ensembl
Cell development Source: Ensembl
Cellular response to hydrogen peroxide Source: Ensembl
Cellular response to trichostatin A Source: Ensembl
Cerebellar cortex development Source: Ensembl
Chromatin organization Source: ProtInc
Chromatin silencing at telomere Source: ARUK-UCL
DNA methylation Source: Ensembl
G1 to G0 transition Source: Ensembl
Hepatocyte homeostasis Source: Ensembl
Hippocampus development Source: Ensembl
Histone H3-K27 methylation Source: UniProtKB
Histone H3-K27 trimethylation Source: Ensembl
Histone methylation Source: UniProtKB
Liver regeneration Source: Ensembl
Negative regulation of cytokine production involved in inflammatory response Source: Ensembl
Negative regulation of DNA-binding transcription factor activity Source: Ensembl
Negative regulation of epidermal cell differentiation Source: Ensembl
Negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
Negative regulation of gene expression, epigenetic Source: UniProtKB
Negative regulation of retinoic acid receptor signaling pathway Source: UniProtKB
Negative regulation of striated muscle cell differentiation Source: Ensembl
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Negative regulation of transcription elongation from RNA polymerase II promoter Source: Ensembl
Positive regulation of cell cycle G1/S phase transition Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of dendrite development Source: Ensembl
Positive regulation of epithelial to mesenchymal transition Source: UniProtKB
Positive regulation of GTPase activity Source: UniProtKB
Positive regulation of MAP kinase activity Source: UniProtKB
Positive regulation of protein serine/threonine kinase activity Source: UniProtKB
Protein localization to chromatin Source: Ensembl
Regulation of circadian rhythm Source: UniProtKB
Regulation of gliogenesis Source: Ensembl
Regulation of transcription, DNA-templated Source: ProtInc
Response to estradiol Source: Ensembl
Response to tetrachloromethane Source: Ensembl
Rhythmic process Source: UniProtKB-KW
Skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: Ensembl
Synaptic transmission, GABAergic Source: Ensembl
Cellular Location
Nucleus. Localizes to the inactive X chromosome in trophoblast stem cells.
Involvement in disease
Weaver syndrome (WVS):
A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand.
PTM
Phosphorylated by AKT1. Phosphorylation by AKT1 reduces methyltransferase activity. Phosphorylation at Thr-345 by CDK1 and CDK2 promotes maintenance of H3K27me3 levels at EZH2-target loci, thus leading to epigenetic gene silencing.
Sumoylated.
Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2 complex.