Characterization of the EZH2-MMSET Histone Methyltransferase Regulatory Axis in Cancer

Irfan A. Asangani, Bushra Ateeq, Qi Cao, Lois Dodson, Mithil Pandhi, Lakshmi P. Kunju, Rohit Mehra, Robert J. Lonigro, Javed Siddiqui, Nallasivam Palanisamy, Yi Mi Wu, Xuhong Cao, Jung H. Kim, Meng Zhao, Zhaohui S. Qin, Mathew K. Iyer, Christopher A. Maher, Chandan Kumar-Sinha, Sooryanarayana Varambally, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)80-93
Number of pages14
JournalMolecular Cell
Volume49
Issue number1
DOIs
StatePublished - Jan 10 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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