期刊
SCIENCE ADVANCES
卷 4, 期 11, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aau6986
关键词
-
资金
- Training Program in Signal Transduction and Cancer [T32 CA070085]
- NIH/NCI [T32CA070085]
- Alex's Lemonade Stand Foundation
- Northwestern Mutual
- NIH [R50CA211428, K08HL128867]
- Francis Family Foundation's Parker B. Francis Research Opportunity Award
- NCI's Outstanding Investigator Award [R35CA197569]
The tet methylcytosine dioxygenase 2 (TET2) enzyme catalyzes the conversion of the modified DNA base 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Here, using newly developed TET2-specific antibodies and the estrogen response as a model system for studying the regulation of gene expression, we demonstrate that endogenous TET2 occupies active enhancers and facilitates the proper recruitment of estrogen receptor alpha (ER alpha). Knockout of TET2 by CRISPR-CAS9 leads to a global increase of DNA methylation at enhancers, resulting in attenuation of the estrogen response. We further identified a positive feedback loop between TET2 and ER alpha, which further requires MLL3 COMPASS at these enhancers. Together, this study reveals an epigenetic axis coordinating a transcriptional program through enhancer activation via DNA demethylation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据