Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility

被引：126

作者：

Lio, Chan-Wang ^{[1
]}

Zhang, Jiayuan ^{[2
,3
]}

Gonzalez-Avalos, Edahi ^{[1
]}

Hogan, Patrick G. ^{[1
]}

Chang, Xing ^{[1
,2
,3
,4
]}

Rao, Anjana ^{[1
,4
,5
,6
]}

机构：

[1] Div Signaling & Gene Express, San Diego, CA USA

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China

[4] Sanford Consortium Regenerat Med, San Diego, CA USA

[5] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA

[6] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA

来源：

ELIFE | 2016年 / 5卷

基金：

美国国家卫生研究院;

关键词：

5-METHYLCYTOSINE OXIDATION; GENE-EXPRESSION; CELL IDENTITY; METHYLATION; PROTEINS; DIFFERENTIATION; ENHANCERS; ROLES; 5-HYDROXYMETHYLCYTOSINE; DEMETHYLATION;

D O I：

10.7554/eLife.18290

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Ig kappa locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Ig kappa 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igx enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igx enhancer function by modulating the modification status of DNA.

引用

页数：26

共 82 条

[81] The Igκ Gene Enhancers, E3′ and Ed, Are Essential for Triggering Transcription [J].