EZH2

EZH2

Target · Histone methyltransferase

EZH2 Enhancer of zeste 2 polycomb repressive complex 2 subunit · Histone-lysine N-methyltransferase EZH2

EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit, also known as KMT6 or KMT6A) is the catalytic subunit of the PRC2/EED-EZH2 complex. It methylates histone H3 to repress transcription, and it is a central enzyme in Polycomb-mediated epigenetic silencing. Browse Assay Genie's current range of EZH2 research reagents below, or read on for the biology behind the target.

Nuclear proteinH3K27 methyltransferaseCatalytic subunit of PRC2
746 aa
Protein length
~85 kDa
Molecular weight
7q36.1
Gene locus
EC 2.1.1.356
Enzyme class
Target information

What is EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit)?

EZH2 is the catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates Lys-9 (H3K9me) and Lys-27 (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The enzyme can mono-, di- and trimethylate Lys-27 to form H3K27me1, H3K27me2 and H3K27me3. It prefers less methylated substrates and loses activity as more methyl groups are added (H3K27me0 > H3K27me1 > H3K27me2). The PRC2/EED-EZH2 complex may also act as a recruiting platform for DNA methyltransferases, linking two epigenetic repression systems.

Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. Compared with EZH1-containing complexes, EZH2 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. EZH2 can also methylate non-histone proteins, including the transcription factor GATA4 and the nuclear receptor RORA. It also regulates the circadian clock: it is essential for CRY1/2-mediated repression of PER1/2 activation by the CLOCK-BMAL1 heterodimer, through di- and trimethylation of H3 Lys-27 at the PER1/2 promoters.

The EZH2 gene encodes a member of the Polycomb-group family, whose complexes maintain the repressive state of genes over successive cell generations. The protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein and the X-linked nuclear protein, and may play a role in the haematopoietic and central nervous systems. The protein belongs to the class V-like SAM-binding methyltransferase superfamily, EZ subfamily. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Earlier names include enhancer of zeste homolog 2 (Drosophila), and the aliases ENX-1 and EZH1 appear in HGNC records.

Epigenetics and chromatin biology

EZH2 writes H3K27me1, H3K27me2 and H3K27me3 marks, making it a core enzyme for studying Polycomb-mediated transcriptional repression.

Stem cell differentiation

EZH2-dependent H3K27me3 is required for embryonic stem cell identity and proper differentiation, and EZH2 is more abundant than EZH1 in these cells.

Circadian clock regulation

EZH2 methylates histone H3 at PER1/2 promoters, supporting CRY1/2-mediated repression of CLOCK-BMAL1 transcriptional activation.

Haematopoietic and neural development

As a Polycomb-group protein, EZH2 may play a role in the haematopoietic and central nervous systems.

Background

EZH2 frequently asked questions

What does EZH2 do?

EZH2 is the catalytic subunit of the PRC2/EED-EZH2 complex. It mono-, di- and trimethylates Lys-27 of histone H3, which leads to transcriptional repression of target genes such as HOXA9 and CDKN2A. It can also methylate non-histone proteins, including GATA4 and RORA.

What other names is EZH2 known by?

EZH2 is also called KMT6 and KMT6A, and ENX-1 and EZH1 are listed as aliases in HGNC. Older names are enhancer of zeste homolog 2 (Drosophila). UniProt names the protein histone-lysine N-methyltransferase EZH2. Multiple transcript variants encoding distinct isoforms have been identified.

How does EZH2 differ from EZH1?

Both are catalytic subunits of PRC2 complexes. EZH2-containing complexes are more abundant in embryonic stem cells and play a major role in forming H3K27me3, needed for stem cell identity and differentiation. A mouse ortholog, Ezh2, exists; check the datasheet of any product for its validated reactivity.

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Related targets

EZH1, the related catalytic subunit of Polycomb repressive complex 2, with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q15910; product specifications from Assay Genie datasheets.

EZH2 Product listing