Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE34886: Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity [expression profiling] GSE34887: Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity [MRE-seq] Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Raja Jothi

PROVIDER: E-GEOD-34267 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.

Freudenberg Johannes M JM Ghosh Swati S Lackford Brad L BL Yellaboina Sailu S Zheng Xiaofeng X Li Ruifang R Cuddapah Suresh S Wade Paul A PA Hu Guang G Jothi Raja R

Nucleic acids research 20111230 8

The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC iden ...[more]

PMID: 22210859

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Project description: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. 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.

Dataset Information

Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity

Publications

Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.

Similar Datasets

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