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Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming

ABSTRACT: Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming

PROVIDER: PRJNA589024 | ENA |

REPOSITORIES: ENA

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Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (RNA-Seq)

Project description:Evolutionarily conserved SCAN domain-containing zinc finger transcription factors (ZSCAN) have been found in both the mouse and human genomes. Of which, Zscan4 is crucial for zygotic genome activation (ZGA) in preimplantation embryos, and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Disruption of the Zscan4f-Tet2 interaction impairs cellular metabolism, proteasome function, and ultimately compromises iPSC generation. These results identify Tet2 as a major cooperator for the function of Zscan4f, and suggest a common mechanism shared by SCAN family transcription factors to recruit TET DNA dioxygenases to regulate diverse cellular processes.

2019-11-13 | GSE140237 | GEO

Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (ChIP-Seq)

2019-11-13 | GSE140236 | GEO

Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (ChIP-Seq)

Project description:Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (ChIP-Seq)

| PRJNA589029 | ENA

Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (RNA-Seq)

Project description:Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming (RNA-Seq)

| PRJNA589034 | ENA

Tet2 interacts with SCAN domain and regulates Zscan4-associated events during cell reprogramming

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-13 | GSE140239 | GEO

OGT, H2B S112GlcNAc, TET2 ChIP-seq results

Project description:TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription starting sites (TSS). Down-regulation of TET2 reduces the amount of H2B S112 GlcNAc marks in vivo, which are associated with gene transcription regulation. We found that OGT interacts with TET2 tightly. Using ChIP-seq with specific antibodies, we tested the co-localization of TET2 and OGT in genome level.

2012-12-11 | E-GEOD-41720 | biostudies-arrayexpress

ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes [ChIP-Seq]

Project description:The Zinc finger and SCAN domain containing 4 (Zscan4) protein, expressed transiently in pluripotent stem cells as well as in gamete and embryonic development, regulates genome stability in addition to telomere elongation and karyotype correction in mouse ES cells. However, the mechanism underlying Zscan4’s ability to counter the toxic effects of DNA/chromatin remodeling is not fully understood. In this study, we used ChIP-seq technology with Zscan4 antibodies to identify genome-wide binding sites in mouse and human ES cells. We discovered that both mouse and human Zscan4 bind to specific simple sequence repeats, (TG/CA)n, that have a propensity to induce genomic instability through a left-handed helix and stem-loop structure. Furthermore, we found that Zscan4 removes active histone marks from (TG/CA)n regions to maintain the closed/inactive chromatin state. These results demonstrate that Zscan4 protects unstable genomic regions by directing chromatin condensation.

2024-01-25 | GSE243626 | GEO

ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes [RNA-Seq]

2024-01-25 | GSE243627 | GEO

CHIP-seq analysis about Histones and Zscan4 after Zscan4 overexpression

Project description:Transcription factor Zscan4 was newly discovered to be a marker of the intermediate state of 2-cell like cells . In addition, the WGCNA discovered a strong positive correlation between the expression of Zscan4 and that of MT2/MERVL .Hence, we examined the possibility for Zscan4 as an activator of MT2/MERVL.

2019-07-08 | GSE125238 | GEO

TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions

Project description:Estrogen receptor-alpha (ER) drives tumour development and metastasis in ER positive (ER+) breast cancer. GATA3 is a transcription factor that has been closely linked to ER function, but the role of GATA3 in ER-transcriptional activity is not clear. We sought to identify the contribution of GATA3 to the ER complex, by conducting quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME), to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, very few proteins were dissociated from the ER complex in the absence of GATA3, with the only major change being loss of TET2 in the ER complex. In breast cancer cells and Patient-Derived Xenograft (PDX) tissue, TET2 binding events were shown to constitute a near-total subset of ER binding events, and loss of TET2 was functionally associated with reduced activation of proliferative pathways. To investigate the TET2-ER relationship, the role of TET2 in regulating DNA modifications in ER+ breast cancer cells was examined. TET2 knockdown did not appear to result in changes to global DNA methylation, however, oxidation of methylated DNA to 5-hydroxymethylcytosine (5hmC) was significantly reduced after TET2 depletion and these events occurred at ER enhancers. These findings implicate TET2 in the production and maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.

2021-02-10 | PXD019438 | Pride

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