EZH2

Protein EZH2 map

Identifiers
enhancer of zeste homolog 2 (Drosophila)
“enhancer of zeste (Drosophila) homolog 2″
HUGO:EZH2 HGNC:3527 ENTREZ:2146 UNIPROT:Q15910 GENECARDS:EZH2 KEGG:2146 ATLASONC:GC_EZH2 WIKI:EZH2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Cell cycle  map  / E2F6  map

References
PMID:22796940
The silencing of E-cadherin expression by hypermethylation is a common event in cancer.
DNMTs target cytosine residues in CpG dinucleotides for methylation and have been identified in the repression of E-cadherin in normal and pathological contexts
such as colorectal cancer, gastric cancer and hepatocellular carcinomas.
Multiple signaling pathways involved in EMT and tumorigenesis activate DNMTs, e.g., ras43 and TGF-b.
DNMTs bind several histone remodeling enzymes, such as Sirtuin and G9a.
However, SNAI1 has been shown to be linked to DNMT1, notably in association with G9a and Suv39H1.
Cooperation between Polycomb proteins and EMT-inducing transcription factors.
The polycomb proteins are part of repressor complexes that inhibit gene expression through chromatin remodeling.
The polycomb repressive complex 2 (PRC2) recruits PRC1 after chromatin methylation at H3K27 through enhancer of EZH2, a histone H3 lysine-27-specific methyltransferase.
Both, PRC1 and PRC2 have been shown to interact with SNAI1 and TWIST1 to promote EMT.
SNAI1 is stabilized through its interaction with the PRC1 component BMI1 and interacts with EZH2 and Suz12 to repress CDH1 expression.
Interestingly, EZH2 also participates in TGFb1 signaling, a potent inducer of EMT.
BMI-1 can also interact with TWIST to induce EMT.
Repression of E-cadherin by SNAI1/TWIST1 involves the recruitment of histone remodeling proteins to the promoter, where SNAI1 interacts with histone deacetylase HDAC1 and HDAC2.
The intricate interactions of EMT-inducing transcription factors and chromatin remodeling complexes PRC1 and PRC2 may offer novel approaches to control EMT and thus cell adhesion in cancer cells via a plethora of new drug, such as HDACs and DNMT inhibitors.

EZH2@Nucleus

References
e_re1185( EMT  map ):
PMID:22796940
Repression of E-cadherin by SNAI1/TWIST1 involves the recruitment of histone remodeling proteins to the promoter, where SNAI1 interacts with histone deacetylase HDAC1 and HDAC2.
PMID:21685935
EZH2 supports carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1 and HDAC2 and Snail to inhibit E-cadherin.


Modifications:
In compartment: Nucleus
  1. EZH2@Nucleus map

Participates in complexes:
In compartment: Nucleus

  1. EZH2:​HDAC1:​HDAC2:​SNAI1@Nucleus map

Participates in reactions:
As Reactant or Product:

  1. DP1*:​E2F6:​EPC1@Nucleus map + EZH2@Nucleus map + EED@Nucleus map map DP1*:​E2F6:​EED:​EPC1@Nucleus map

  2. EZH2@Nucleus map + SNAI1@Nucleus map + HDAC1@Nucleus map + HDAC2@Nucleus map map EZH2:​HDAC1:​HDAC2:​SNAI1@Nucleus map
  3. rEZH2@Nucleus map map EZH2@Nucleus map

As Catalyser:

  1. gE-Cadherin*@Nucleus map map rE-Cadherin*@Nucleus map

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