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ULI-NChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs [ChIP-seq]

ABSTRACT: Our study demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.

ORGANISM(S): Mus musculus

PROVIDER: GSE159552 | GEO | 2021/01/01

REPOSITORIES: GEO

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RNA-seq Analysis of Wild Type(WT) and Dcaf11 overexpression (OE) ESCs

Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we show that Dcaf11 (Ddb1- and Cul4-associated factor 11) participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs). The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is also greatly compromised. Mechanistically, Dcaf11 targets Kap1 (KRAB-associated protein 1) for ubiquitination-mediated degradation, leading to the activation of Zscan4 downstream enhancer and the removal of heterochromatic H3K9me3 at telomere/subtelomere regions. Our study therefore demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.

2021-07-17 | GSE180259 | GEO

Single cell RNA-seq Analysis of Wild Type(WT), Dcaf11 knockout(KO) and Dcaf11 knockdown(KD) embryos

Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis through the so-called alternative lengthening of telomere (ALT) mechanism. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we showed that Dcaf11 participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs) in a telomerase-independent manner. The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is greatly compromised. Mechanistically, DCAF11 reactivates Zscan4 and facilitates the removal of heterochromatic H3K9me3 at telomere/subtelomere regions through targeting TRIM28 for ubiquitination-mediated degradation. Our study therefore demonstrates that the ALT factor Dcaf11 plays important roles in telomere elongation in early embryos and ESCs.

2021-01-01 | GSE132745 | GEO

ULI-NChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs [ChIP-seq]

Project description:ULI-NChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs [ChIP-seq]

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Kap1 ChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs

Project description:ESC Kap1 profiles of WT and Dcaf11 OE were generated by deep sequencing, using Illumina GAIIx.

2021-01-01 | GSE162232 | GEO

Dcaf11 facilitates telomere elongation in early embryos and embryonic stem cells (ESCs) through activating the Zscan4-mediated alternative lengthening telomere (ALT) mechanism

Project description:Dcaf11 facilitates telomere elongation in early embryos and embryonic stem cells (ESCs) through activating the Zscan4-mediated alternative lengthening telomere (ALT) mechanism

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Kap1 ChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs

Project description:Kap1 ChIP-seq Analysis of Wild Type(WT) and Dcaf11 overexpresion(OE) ESCs

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RNA-seq Analysis of Wild Type(WT) and Dcaf11 overexpression (OE) ESCs

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Expression data of the control and CITED1 OE ESCs

Project description:Trophoblast lineages, as the precursor of placenta, are essential for post-implantation embryo survival. However, the regulatory networks for trophoblast development remains incompletely understood. Here, we identified CITED1 as a regulator to induce trophoblast-like differentiation from mESCs. Overexpression of CITED1 in ESCs prompted differentiation towards trophoblast accompanying with elevated expression of trophoblast marker genes. To evaluate the ability of CITED1 to induce trophoblast differentiation at a genome-wide scale, we compared the global transcriptional profiles between CITED1 overexpressing cells and control ESCs by Affymetrix microarray analysis at day 1 and day 2 after transfection. We used microarrays to identify genes affected by CITED1 overexpression in mouse ESCs.

2018-09-01 | GSE103414 | GEO

Genome-wide DNA methylation analyses by the MeDIP assay

Project description:We analyzed the genome-wide DNA methylation in Zscan4 overexpressing ES cells. Zscan4 overexpression induced slight DNA demethylation in telomere and major satellite regions. Subsequent genome-wide analysis of non-repeated regions revealed the significant reduction of DNA methylation at Zscan4-dependent hyperacetylation sites. This result indicates that Zscan4 is not only a marker of the Zscan4+ state of ES cells, but also indispensable for the dramatic epigenetic modifications occurring in the Zscan4+ state. DNA methylation in Zscan4 overexresssing ES cells

2015-09-10 | E-GEOD-58618 | biostudies-arrayexpress

Dynamics of Telomere Rejuvenation During Chemical Induction to Pluripotent Stem Cells

Project description:Chemical induced pluripotent stem cells (CiPSCs) have been successfully achieved and may provide an alternative and attractive source for stem cell-based therapy. Sufficient telomere lengths are critical for unlimited self-renewal and genomic stability of pluripotent stem cells. Dynamics of telomere reprogramming and whether and how telomeres are sufficiently elongated in the CiPSCs have remained to be understood. We show that CiPSCs acquire telomere lengthening with increasing passages after clonal formation. Both telomerase activity and recombination-based mechanisms are involved in the telomere elongation. Telomere lengths strongly indicate the degree of reprogramming, pluripotency and differentiation capacity of CiPSCs. Nevertheless, telomere damage and shortening occur at late stage of lengthy induction, limiting CiPSC formation. Recombination mechanism is not activated during induction until CiPSC clonal formation and passages. We find that histone crotonylation induced by crotonic acid can activate two-cell genes including Zscan4, alleviate telomere damage and shortening during induction and promote CiPSC generation. Moreover, crotonylation decreases abundance of heterochromatic H3K9me3 and HP1a at subtelomeres and Zscan4 loci. Taken together, telomere rejuvenation links to reprogramming and pluripotency of CiPSCs. Crotonylation facilitates telomere maintenance and enhances chemical induced reprogramming to pluripotency.

2018-05-01 | GSE113921 | GEO

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