Publication

Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer.

Mol Cell. 2013 Jan 10;49(1):80-93. doi: 10.1016/j.molcel.2012.10.008. Epub 2012 Nov 15.

Abstract

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.

Authors

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.

Institute Authors

Christopher Maher, Ph.D.