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TET2 coactivates gene expression through demethylation of enhancers.

Abstract：

: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 α (ERα). 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 ERα, 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.

journal_name

Sci Adv

journal_title

Science advances

authors

Wang L,Ozark PA,Smith ER,Zhao Z,Marshall SA,Rendleman EJ,Piunti A,Ryan C,Whelan AL,Helmin KA,Morgan MA,Zou L,Singer BD,Shilatifard A

doi

10.1126/sciadv.aau6986

subject

Has Abstract

pub_date

2018-11-07 00:00:00

pages

eaau6986

issue

11

issn

2375-2548

pii

aau6986

journal_volume

4

pub_type

杂志文章

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