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Status |
Public on Mar 30, 2011 |
Title |
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells (ChIP-Seq) |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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.
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Overall design |
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.
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Contributor(s) |
Wu H, D'Alessio A, Ito S, Xia K, Wang Z, Zhao K, Sun Y, Cui K, Zhang Y |
Citation(s) |
21451524, 21460036 |
Submission date |
Jan 24, 2011 |
Last update date |
May 15, 2019 |
Contact name |
Hao Wu |
E-mail(s) |
haowu7@gmail.com
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Phone |
617-713-8660
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Organization name |
Harvard Medical School/HHMI
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Department |
Genetics
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Lab |
Yi Zhang
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Street address |
149G Warren Alpert Building, 200 Longwood Avenue
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City |
Boston |
State/province |
Massachusetts |
ZIP/Postal code |
02115 |
Country |
USA |
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Platforms (1) |
GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE26833 |
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells |
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Relations |
SRA |
SRP005456 |
BioProject |
PRJNA142019 |