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Title: 
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells (ChIP-Seq)
Measurement Type: 
Transcription Factor Binding (ChIP-Seq)
Factors: 
Genetic Characteristics
Summary: 
Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity. Recent demonstration that members of the Ten-eleven translocation (Tet) family proteins can convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state. We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell self-renewal and maintenance. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq), here we show that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite a general increase in levels of DNA methylation at Tet1 binding-sites, Tet1 depletion does not lead to down-regulation of all the Tet1 targets. Interestingly, while Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also required for repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators. To determine the genome-wide distribution of Tet1 in mouse ES cells, we have performed ChIP-seq experiments using Tet1 antibodies in control knockdown (KD) and Tet1 KD ES cells.
Contact(s): 
Curator(s): 
mmerrill

Group

Citations: 
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells.
Wu H, D'Alessio AC, Ito S, Xia K, Wang Z, Cui K, Zhao K, Sun YEve, Zhang Y
Nature. 2011 May 19; 473(7347):389-93. PMID: 21451524. Abstract
Download: 
Study metadata (ISA-Tab: isa_16114_676360.zip)