EZH2
GeneName
EZH2
Summary
EZH2, also known as EZH-2, Enx1, or ENX-1, is an 85kDa protein that functions as a histone methyltransferase, primarily involved in the trimethylation of histone H3 at lysine 27 (H3K27me3), a mark associated with transcriptional repression. It is a core component of the Polycomb Repressive Complex 2 (PRC2), which plays a critical role in chromatin organisation and gene silencing. EZH2 is predominantly expressed in the nucleus and is associated with various subcellular structures, including chromatin, nucleoplasm, and heterochromatin. Its activity is essential for processes such as B cell differentiation, cardiac muscle hypertrophy, and cellular responses to stressors. Additionally, EZH2 is implicated in the regulation of stem cell differentiation and various developmental processes, including cerebellar cortex and hippocampus development.
Importance
EZH2 is relevant to: - Cancer research, particularly in the context of its role in promoting oncogenesis through epigenetic silencing of tumour suppressor genes. - Stem cell biology, as it regulates differentiation and maintenance of pluripotency. - Inflammatory responses, due to its involvement in the negative regulation of cytokine production. - Neurodevelopmental disorders, given its role in brain development and synaptic transmission. - Cardiovascular research, as it is implicated in cardiac muscle responses to stress and hypertrophy.
Top Products
For researchers investigating EZH2, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-KMT6 / EZH2 antibody (ab186006), which has garnered 94 citations and is highly regarded for its performance in Western blotting (WB), immunohistochemistry (IHC), and immunoprecipitation (IP). This antibody is a trusted choice for those studying EZH2 in various contexts.Additionally, we offer the recombinant antibody, Anti-KMT6 / EZH2 antibody [EPR20108] - ChIP Grade (ab191250). This product has been validated in knockout models and is suitable for Western blotting (WB), chromatin immunoprecipitation (ChIP), and immunoprecipitation (IP). With 62 citations, it demonstrates a solid reputation in the research community. The recombinant nature of this antibody ensures batch-to-batch consistency, making it an ideal option for researchers requiring reliable and reproducible results in their studies of EZH2.
Abcam Product Citation Summary
The data indicates that EZH2 is being studied in various human cancer contexts, particularly in breast cancer and acute myeloid leukaemia (AML). The use of Abcam antibodies in Western blotting highlights the importance of EZH2 in cancer biology, including its regulation and interaction with other RNA molecules. Additionally, studies involving domestic dogs and mouse tumour tissues suggest a broader relevance of EZH2 across species in cancer research.
Abcam Product Citation Table
Developmental stage
Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary.
Function
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-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.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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.
Sequence Similarities
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. EZ subfamily.
Tissue Specificity
In the ovary, expressed in primordial follicles and oocytes and also in external follicle cells (at protein level) (PubMed:31451685). Expressed in many tissues (PubMed:14532106). Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis (PubMed:14532106).
Cellular localization
- Nucleus
- Localizes to the inactive X chromosome in trophoblast stem cells.
Alternative names
KMT6, EZH2, Histone-lysine N-methyltransferase EZH2, ENX-1, Enhancer of zeste homolog 2, Lysine N-methyltransferase 6
Database links
swissprot:Q15910 omim:602923 swissprot:Q15022 swissprot:Q09028 swissprot:Q6ZN18 entrezGene:2146 entrezGene:8726 entrezGene:5928 entrezGene:23512 entrezGene:121536 omim:601573 omim:606245 omim:605984 swissprot:O75530
Other research areas
- Immuno-oncology
- Oncology