DNA Methylation and SETDB1/H3K9me3 Regulate Predominantly Distinct Sets of Genes, Retroelements, and Chimeric Transcripts in mESCs

被引：391

作者：

Karimi, Mohammad M. ^{[1
]}

Goyal, Preeti ^{[1
]}

Maksakova, Irina A. ^{[1
]}

Bilenky, Misha ^{[2
]}

Leung, Danny ^{[1
]}

Tang, Jie Xin ^{[1
]}

Shinkai, Yoichi ^{[3
,4
]}

Mager, Dixie L. ^{[1
,5
]}

Jones, Steven ^{[2
]}

Hirst, Martin ^{[2
]}

Lorincz, Matthew C. ^{[1
]}

机构：

[1] Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada

[2] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[3] Kyoto Univ, Inst Virus Res, Sakyo Ku, Expt Res Ctr Infect Dis, Kawara, Kyoto 6068507, Japan

[4] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kawara, Kyoto 6068507, Japan

[5] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada

来源：

CELL STEM CELL | 2011年 / 8卷 / 06期

关键词：

EMBRYONIC STEM-CELLS; ENDOGENOUS RETROVIRUSES; TRANSPOSABLE ELEMENTS; HISTONE H3; RNA-SEQ; CHROMATIN; GENOME; PARALLEL; COMPLEX; RETROTRANSPOSON;

D O I：

10.1016/j.stem.2011.04.004

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

DNA methylation and histone H3 lysine 9 trimethylation (H3K9me3) play important roles in silencing of genes and retroelements. However, a comprehensive comparison of genes and repetitive elements repressed by these pathways has not been reported. Here we show that in mouse embryonic stem cells (mESCs), the genes upregulated after deletion of the H3K9 methyltransferase Setdb1 are distinct from those derepressed in mESC deficient in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b, with the exception of a small number of primarily germline-specific genes. Numerous endogenous retroviruses (ERVs) lose H3K9me3 and are concomitantly derepressed exclusively in SETDB1 knockout mESCs. Strikingly, similar to 15% of upregulated genes are induced in association with derepression of promoter-proximal ERVs, half in the context of "chimeric" transcripts that initiate within these retroelements and splice to genic exons. Thus, SETDB1 plays a previously unappreciated yet critical role in inhibiting aberrant gene transcription by suppressing the expression of proximal ERVs.

引用

页码：676 / 687

页数：12

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