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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 30, 2011 |
| Title |
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells (ChIP-chip and MeDIP-chip) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
Methylation profiling by genome tiling array
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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 |
Chromatin or genomic DNA extracted from control (Con) or Tet1 knockdown (KD) mouse ES cells was immunoprecipitated with indicated antibodies and analyzed by NimbleGen 2.1M mouse whole genome tiling microarrays (a 4-array set covering the entired non-repetitive portion of mouse genome). Whole cell extract (WCE) was used as input controls in IP/input experiments. In IP/IP experiments, immunoprecipitated DNA from Con KD and Tet1 KD ES cells was directly compared on the same microarrays.
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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 |
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| Submission date |
Jan 24, 2011 |
| Last update date |
Jun 22, 2012 |
| Contact name |
Hao Wu |
| E-mail(s) |
[email protected]
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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 (4)
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| GPL7523 |
NimbleGen mouse (mm8) whole genome tiling array 1 of 4 [2007-08-17_MM8_Economy_01] |
| GPL7524 |
NimbleGen mouse (mm8) whole genome tiling array 2 of 4 [2007-08-17_MM8_Economy_02] |
| GPL7525 |
NimbleGen mouse (mm8) whole genome tiling array 3 of 4 [2007-08-17_MM8_Economy_03] |
| GPL7526 |
NimbleGen mouse (mm8) whole genome tiling array 4 of 4 [2007-08-17_MM8_Economy_04] |
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| Samples (20)
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| GSM659630 |
Con KD ES cells, DNA methylation by MeDIP-chip (1/4) |
| GSM659631 |
Con KD ES cells, DNA methylation by MeDIP-chip (2/4) |
| GSM659632 |
Con KD ES cells, DNA methylation by MeDIP-chip (3/4) |
| GSM659633 |
Con KD ES cells, DNA methylation by MeDIP-chip (4/4) |
| GSM659634 |
Tet1 KD ES cells, DNA methylation by MeDIP-chip (1/4) |
| GSM659635 |
Tet1 KD ES cells, DNA methylation by MeDIP-chip (2/4) |
| GSM659636 |
Tet1 KD ES cells, DNA methylation by MeDIP-chip (3/4) |
| GSM659637 |
Tet1 KD ES cells, DNA methylation by MeDIP-chip (4/4) |
| GSM659638 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (1/4), exp1 |
| GSM659639 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (2/4), exp1 |
| GSM659640 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (3/4), exp1 |
| GSM659641 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (4/4), exp1 |
| GSM659642 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (1/4), exp2 |
| GSM659643 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (2/4), exp2 |
| GSM659644 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (3/4), exp2 |
| GSM659645 |
Con KDvsTet1 KD ES cells, DNA methylation by MeDIP-chip (4/4), exp2 |
| GSM659646 |
Con KDvsTet1 KD ES cells, Ezh2 ChIP-chip (1/4) |
| GSM659647 |
Con KDvsTet1 KD ES cells, Ezh2 ChIP-chip (2/4) |
| GSM659648 |
Con KDvsTet1 KD ES cells, Ezh2 ChIP-chip (3/4) |
| GSM659649 |
Con KDvsTet1 KD ES cells, Ezh2 ChIP-chip (4/4) |
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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 |
| BioProject |
PRJNA142015 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26827_RAW.tar |
2.3 Gb |
(http)(custom) |
TAR (of PAIR, TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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