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
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90985 | GEO | 2017/12/07
SECONDARY ACCESSION(S): PRJNA356552
REPOSITORIES: GEO
Similar Datasets
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
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
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 | GSE205041 | GEO
Project description: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
2011-11-07 | E-GEOD-31183 | biostudies-arrayexpress
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.
2011-11-07 | GSE31181 | GEO
Project description:Selective maintenance of genomic methylation imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions (ICRs) in early mouse embryos and ES cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. In addition, several cases of human transient neonatal diabetes (TND) are associated with somatic mutations in ZFP57 coding sequence. Here we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice assigning allele specificity to approximately two thirds of all binding sites. While half of these are biallelic and include ERV targets, the rest show mono-allelic binding based either on parental-origin or on genetic background of the allele. Parental-origin allele-specific binding was methylation-dependent and mapped only to imprinted DMRs established in the germline (gDMRs). No binding was evident at secondary somatically-derived DMRs. ZFP57-bound gDMRs can predict imprinted gene expression and we identify new imprinted genes, including the Fkbp6 gene with a critical function in mouse male germ cell development. Genetic-background specific sequence differences also influence ZFP57 binding. We show that genetic variation that disrupts the consensus binding motif and its methylation is associated with mono-allelic expression of neighbouring genes. The work described here uncovers further roles for ZFP57 mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined mono-allelic gene expression. Input and Zfp57 CHiP-Seq profiles of hybrid Black6/Cast ES cells were generated by sequencing using the Illumina GAIIx platform.
2015-05-08 | E-GEOD-55382 | biostudies-arrayexpress
Project description:KRAB-zinc finger proteins (KZFPs) represent one of the largest families of DNA binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. However, one member, ZFP57, is required to maintain the post-fertilization DNA methylation memory of parental-origin at genomic imprints. We have conducted RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant ES cells to characterize the targets of ZFP57 in more detail. Over 80% of ZFP57 targets are TEs. However, mutants indicate that ZFP57 is not essential for their repression in ES cells. The remaining targets lie within unique imprinted and non-imprinted sequences. Though loss of ZFP57 influences imprinted genes as expected, the majority of unique gene targets lose H3K9me3 with little effect on DNA methylation and with very few exhibiting alterations in expression. Furthermore, comparison with DNA methyltransferase-deleted ES cells (TKO) identifies remarkably similar losses of H3K9me3 and changes in expression, defining regions where H3K9me3 is secondary to DNA methylation. We determine that ZFP57 is the principal methylation-sensitive KZFP recruiting KAP1 and H3K9me3 in ES cells. Finally, like imprints, other unique targets of ZFP57 are enriched for germline-derived DNA methylation including oocyte-specific methylation that is resistant to post-fertilisation epigenetic reprogramming. Our analyses suggest the evolution of a DNA methylation sensitive KZFP, that may serve to reinforce the silenced state at TEs, but whose primary function is to maintain DNA methylation and repressive histone marks at imprinted regions.
2019-08-21 | GSE123942 | GEO
Project description:We did RNA-seq analysis to compare gene expression profiles in mouse embryos with or without ZFP57. We also perfromed whole-genome bisulfite sequencing analysis (WGBS) for the Zfp57 mutant mouse embryos and control heterozygous embryos. We analyzed DNA methylation at the imprinting control regions (ICRs), differentially methylation regions (DMRs) and repetitive elements including LINE-1, LINE-2, SINE, LTR and IAP.
2021-01-27 | GSE165079 | GEO
Project description:ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required.
2016-06-04 | GSE77444 | GEO
Project description:ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required.
2016-06-04 | GSE77440 | GEO