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ZFP57/KAP1 recognize a methylated hexanucleotide to affect the chromatin and DNA methylation of imprinting control regions in embryonic stem cells

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE31181: ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells GSE31182: RNA-seq and expression profile of WT and ZFP57 KO ES cells Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Simon Quenneville

PROVIDER: E-GEOD-31183 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells

Project description:We have performed ChIP seq analysis to obtain the positions of KAP1 and ZFP57 binding sites in mouse ES cells. By comparing the two lists, we were able to find bona fide sites. ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells

2011-11-07 | E-GEOD-31181 | biostudies-arrayexpress

ChIP-seq analysis of KAP1 and H3K9me3 modifications in mouse spleen B cells

Project description:Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis. Examination of KAP1 binding sites and H3K9me3 enriched regions in KAP1 wild type and KO mouse B splenocytes.

2012-05-16 | E-GEOD-36850 | biostudies-arrayexpress

ChIP-seq analysis of KAP1 binding and H3K9me3 modifications in mouse T cell progenitors

Project description:Chromatin remodelling at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by Kruppel-Associated Box (KRAB)- Associated Protein 1 (KAP1), the universal cofactor of KRAB-zinc finger proteins (-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1-deleted mice displayed a significant expansion of immature thymocytes, imbalances in CD4+/CD8+ cell ratios and impaired responses to TCR stimulation when compared to littermate KAP1 control mice. Transcriptome and chromatin studies revealed that KAP1 binds T cell-specific cis-acting regulatory elements marked by the H3K9me3 repressive mark and enriched in Ikaros/NuRD complexes. Also, KAP1 directly controls the expression of several genes involved in TCR and cytokine signalling. Among these, regulation of FoxO1 seems to play a major role in this system. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB-ZFPs are selectively expressed in T lymphoid cells. These results reveal the so-far unsuspected yet important role of KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation. Examination of KAP1 binding sites and H3K9me3-enriched regions in wild type and KAP1 KO mouse thymocytes.

2012-12-16 | E-GEOD-38579 | biostudies-arrayexpress

ChIP-Seq of HA tagged ZFP57 and KAP1 in mouse ES cells

2011-11-07 | GSE31181 | GEO

KAP1 regulates gene networks controlling B lymphoid cell differentiation and function

Project description:This SuperSeries is composed of the following subset Series: GSE34446: Gene expression analysis of wild type and KAP1 KO splenic B cells GSE36850: ChIP-seq analysis of KAP1 and H3K9me3 modifications in mouse spleen B cells Refer to individual Series

2012-05-16 | E-GEOD-36880 | biostudies-arrayexpress

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2012-08-07 | E-GEOD-38580 | biostudies-arrayexpress

The mismatch-repair proteins MSH2 and MSH6 interact with the imprinting control regions through the ZFP57-KAP1 complex (RRBS)

Project description:Genomic imprinting is controlled by CpG-rich regions (ICRs) acquiring differential methylation in the female and male germline and maintaining it in a parental origin-specific manner in somatic cells. Despite their expected mutation rate due to spontaneous deamination of methylated cytosines, ICRs maintain their CpG-richness and show conservation of CpG-bearing transcription binding sites in mammals. In order to gain further insights into the mechanisms of maintenance of methyl CpGs, we sought to identify the proteins interacting with the methylated allele of the ICRs, by determining the interactors of ZFP57 that recognizes a specific methylated ICR motif in mouse ESCs. Several proteins including factors involved in mRNA processing/splicing, chromatin organization, transcription and DNA repair were identified through a tagged approach coupled to LC–MS/MS analysis. The demonstration of the components of the post-replicative mismatch-repair (MMR) complex as ZFP57 interactors prompted us to investigate the DNA binding profile of MSH2 and MSH6 by chromatin immunoprecipitation and sequencing. We found that these proteins were enriched at the methylated allele of the ICRs and their binding was mediated by the ZFP57/KAP1 complex, suggesting that the MMR complex is recruited to these loci to preserve their genetic integrity.

2022-08-16 | GSE205042 | GEO

The intracellular mediators of the BMP pathway SMAD1/5 bind the Imprinting Control Regions through interaction with the ZFP57/KAP1 complex and contribute to maintain their DNA methylation and H3K9me3 in mouse embryonic stem cells

Project description:We report that SMAD1/5 bind the ICRs by interacting with the ZFP57/KAP1 complex and that this is necessary for the proper maintenance of methylation imprints in mESCs

2017-12-07 | GSE90985 | GEO

The mismatch-repair proteins MSH2 and MSH6 interact with the imprinting control regions through the ZFP57-KAP1 complex (ChIP-Seq)

2022-08-16 | GSE205041 | GEO

ZFP57 recognizes multiple and closely spaced sequence motif variants to maintain repressive epigenetic marks in mouse embryonic stem cells

Project description:In mouse embryonic stem cells SNPs disrupting closely-spaced hexanucleotide motifs are associated with lack of ZFP57 binding and H3K9me3 enrichment. Examination of ZFP57-KAP1 allele-specific binding in two lines of mouse embryonic stem cells JB1 and BJ1 generated from F1 hybrids derived from JF1 x B6 and B6 x JF1 crosses respectively.

2015-11-06 | E-GEOD-74757 | biostudies-arrayexpress

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