Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer.
Asangani IA, Ateeq B, Cao Q, Dodson L, Pandhi M, Kunju LP, Mehra R, Lonigro RJ, Siddiqui J, Palanisamy N, Wu YM, Cao X, Kim JH, Zhao M, Qin ZS, Iyer MK, Maher CA, Kumar-Sinha C, Varambally S, Chinnaiyan AM.
Cancer Research/Cell Biology
Cells used in publication:
Epithelial, prostate (PrEC), human
Tissue Origin: prostate
Mammary Epithelial Cell Growth Medium
Histone methyltransferases (HMTases), as chromatin modifiers, regulate the transcriptomic landscape in normal development as well in diseases such as cancer. Here, we molecularly order two HMTases, EZH2 and MMSET, that have established genetic links to oncogenesis. EZH2, which mediates histone H3K27 trimethylation and is associated with gene silencing, was shown to be coordinately expressed and function upstream of MMSET, which mediates H3K36 dimethylation and is associated with active transcription. We found that the EZH2-MMSET HMTase axis is coordinated by a microRNA network and that the oncogenic functions of EZH2 require MMSET activity. Together, these results suggest that the EZH2-MMSET HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis and may represent an attractive therapeutic target in cancer.
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