Polycomb proteins establish facultative heterochromatin
EZH2 in cancer
Ezh2 deficiency and hyperactivity are implicated in human cancer. EZH2 inactivation is most common to hematological malignancies
Hyperactivity:
- Epithelial cancers such as prostate cancer
- diffuse large B-cell lymphoma (DLBCL)
- Follicular lymphoma
- myeloid dysplastic syndrome (MDS)
- myeloproliferative neoplasm (MPN)
- CALM-AF0 leukemia
- T-lineage acute lymphoblastic leukemia (ALL)
- early T cell precursor (ETP)-ALL
Murine models of EZH2 deficiency
- Inactivation leads to T-cell leukemia
- EZH2 required for T- and B- cell development
- Partially compensated for by EZH1
- In contrast, Eed KO leads to complete loss of PRC2 function and H3K27me2/3 enrichment