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

被引：131

作者：

Asangani, Irfan A. ^{[1
,2
]}

Ateeq, Bushra ^{[1
,2
]}

Cao, Qi ^{[1
,2
]}

Dodson, Lois ^{[1
]}

Pandhi, Mithil ^{[1
]}

Kunju, Lakshmi P. ^{[1
,2
,4
]}

Mehra, Rohit ^{[1
,2
]}

Lonigro, Robert J. ^{[1
,4
]}

Siddiqui, Javed ^{[1
,2
]}

Palanisamy, Nallasivam ^{[1
,2
]}

Wu, Yi-Mi ^{[1
,2
]}

Cao, Xuhong ^{[1
,5
]}

Kim, Jung H. ^{[1
]}

Zhao, Meng ^{[7
]}

Qin, Zhaohui S. ^{[7
]}

Iyer, Mathew K. ^{[1
,6
]}

Maher, Christopher A. ^{[1
,6
]}

Kumar-Sinha, Chandan ^{[1
,2
]}

Varambally, Sooryanarayana ^{[1
,2
,4
]}

Chinnaiyan, Arul M. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[7] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

来源：

MOLECULAR CELL | 2013年 / 49卷 / 01期

关键词：

GROUP PROTEIN EZH2; T(4/14) MULTIPLE-MYELOMA; PROSTATE-CANCER; SOMATIC MUTATIONS; BREAST-CANCER; STEM-CELLS; GENE EZH2; POLYCOMB; EXPRESSION; METHYLATION;

D O I：

10.1016/j.molcel.2012.10.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：80 / 93

页数：14

共 53 条

[1]

Histone methyltransferases in cancer [J].