MERVL/Zscan4 network activation results in transient genome-wide DNA demethylation of mESCs
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PROVIDER: PRJEB15553 | ENA |
REPOSITORIES: ENA
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Project description:Several previous studies have noted a rare sub-population of murine Embryonic Stem Cells (mESCs) which seem to express genes otherwise specific to the 2-cell stage of embryonic development. Here we sorted single cells from a MERVL/Zscan4 reporter line to investigate the continuum of expression as cells go from the standard state to this 2C-like state.
2016-09-30 | E-MTAB-5058 | biostudies-arrayexpress
Project description:Mouse embryonic stem cells are heterogeneous and contain rare cells expressing transcripts normally upregulated in pre-implantation embryos, including the Zscan4 cluster and MuERVL endogenous retrovirus. Through single cell transcriptomics and genome-wide chromatin and DNA methylation analyses we uncover the dynamics of the regulation and epigenetic consequences of these transient cells. Transcriptional activation of MuERVL and Zscan4 coincided with a global increase in chromatin accessibility. Through a combination of bulk and single-cell RNA-sequencing, we reveal the dynamics and specificities of a MuERVL driven transcriptional network. Interestingly, in addition to pre-implantation embryos, the MuERVL network is similarly upregulated during somatic cell reprogramming, associating it with dramatic chromatin remodeling events. In MuERVL+ mESCs, upregulation of a cluster of Eif1A-like genes results in inhibition of protein synthesis, uncoupling transcription from translation. Consequently, depletion of proteins including DNA methyltransferases, results in genome-wide DNA demethylation, demonstrating the influence of endogenous retroviral activation on the host epigenome.
2016-10-03 | GSE85776 | GEO
Project description: Not available
| S-EPMC5055476 | biostudies-literature
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
Project description:MERVL/Zscan4 network activation results in transient genome-wide DNA demethylation of mESCs
| PRJNA339313 | ENA
Project description:Transcription factor Zscan4 was newly discovered to be a marker of the intermediate state of 2-cell like cells . In addition, 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.
2023-06-30 | GSE180003 | GEO
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 | GSE120998 | GEO
Project description:The ERK5 MAP kinase signalling pathway was recently discovered as a driver of naïve pluripotency in mouse Embryonic Stem Cells (mESCs). However, the molecular functions of ERK5 in mESCs have not been investigated. Here, we employ combinatorial mESC proteomics to identify ERK5 target genes and substrates. Global proteomic profiling reveals ZSCAN4 and other 2-cell stage genes as transcriptional targets of the ERK5 pathway. ZSCAN4 expression is specifically induced by ERK5-dependent transcription of the core pluripotency factor KLF2. Additionally, ERK5 directly phosphorylates tandem KLF2 Thr-Pro/Ser-Pro motifs identified by phosphoproteomics to recruit the FBXW7-CUL1 E3 ligase, promoting KLF2 ubiquitylation and degradation. ERK5 phosphorylation of KLF2 thereby provides negative-feedback control to restrain transcriptional induction of ZSCAN4. Our data uncover an auto-regulatory module by which ERK5 co-opts KLF2 to pattern ZSCAN4 expression. This study provides the first molecular insight into ERK5 functions in mESCs, and suggests a novel role for ERK5 signalling in stem cell rejuvenation
2021-11-29 | PXD010581 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. Repetitive sequences such as telomeres, centromeres, and retrotransposons are packed in permanently-condensed and transcriptionally-silenced heterochromatin, whose maintenance is critical for the genome stability. We have recently found that mouse ES cells occasionally go through a unique cell state marked by the transient expression of Zscan4, which plays a key role in long-term genome stability. Here we report our unexpected and counterintuitive finding that the Zscan4+ state is accompanied by a Zscan4-mediated rapid activation and repression of heterochromatin: the burst of transcription from heterochromatin coincided with its transient histone hyperacetylation and DNA demethylation, the clustering of pericentromeric heterochromatin in the perinucleolar region, and the accumulation of chromatin remodeling complexes for both activation (HATs, SWI/SNF) and repression (HDACs, LSD1/KDM1A, NuRD) on heterochromatin. Overall, these findings suggest that ES cells maintain their extraordinary genome stability and immortality by transiently taking extreme measures – a usually forbidden transition to the activated state of heterochromatin. Refer to individual Series
2015-09-10 | E-GEOD-51682 | biostudies-arrayexpress
Project description:The gold standard for examining pluripotency of stem cells is to see whether cells can contribute to entire body of animals. Here we show that the increased frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into 4N blastocyst at unusually high success rate. Although Zscan4-activated cells express genes that are also expressed in 2-cell stage mouse embryos, transiently Zscan4-activated state of ES cells is not associated with the high potency of ES cells. It is thus concluded that ES cells acquire higher potency by going through transient Zscan4 activation state more frequently than the regular state. Taken together, our results indicate that frequent activation of Zscan4 can rejuvenate pluripotent stem cells. Previously, we have shown that constitutive and strong expression of Zscan4 arrest the proliferation of ES cells (refs). We sought for the system to mimic the transient expression of Zscan4 and decided to use ERT2 - Tamoxifen-inducible system (refs). The system allows one to keep a transgene off in the absence of Tmx and turn on in the presence of Tmx at will (refs). We first made a plasmid construct pCAG-Zscan4-ERT2, in which ZSCAN4 ORF fused with ERT2 domain can be driven by a strong ubiquitous promoter CAG. To further investigate this, we transfected pCAG-Zscan4-ERT2 plasmid into an F1 hybrid (C57BL/6J vs. 129) ES cell line V6.5 and isolated multiple cell clones. Based on the qRT-PCR analysis of Zscan4 ORF, we found that cell clones showed a variety of Zscan4 expression levels. We selected the clone that showed the highest Zscan4 expression levels (clone #18) and a clone #2 with the background Zscan4 level.
2013-06-12 | E-GEOD-26162 | biostudies-arrayexpress