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RNA-seq and expression profile of WT and ZFP57 KO ES cells

ABSTRACT: RNA-seq and expression profile of WT and ZFP57 KO ES cells RNA was extracted from both cell lines, PolyA RNA were extracted and RNA-seq was performed

ORGANISM(S): Mus musculus

SUBMITTER: Simon Quenneville

PROVIDER: E-GEOD-31182 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Quenneville Simon S Verde Gaetano G Corsinotti Andrea A Kapopoulou Adamandia A Jakobsson Johan J Offner Sandra S Baglivo Ilaria I Pedone Paolo V PV Grimaldi Giovanna G Riccio Andrea A Trono Didier D

Molecular cell 20111101 3

The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DNMTs leads to ICR DNA demethylation. Accordingly, we find that ZFP57 and KAP1 associated with DNMTs a ...[more]

PMID: 22055183

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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

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

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

RNA-seq and expression profile of WT and ZFP57 KO ES cells

Project description:RNA-seq and expression profile of WT and ZFP57 KO ES cells

2011-11-07 | GSE31182 | GEO

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

2011-11-07 | GSE31181 | 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.

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Allele-specific binding of ZFP57 in the regulation of imprinted and mono-allelic expression

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.

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ZFP57 dictates allelic expression switch of target imprinted genes

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

Zfp57 exerts maternal and sexually dimorphic effects on genomic imprinting

Project description:RNA-seq analysis was used to find the target genes of Zfp57 in mouse embryos.

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RNA seq in two lines of E14 mouse embryonic stem cells

Project description:This experiment was designed to obtain the polyA+ transcriptome in E14 ESCs PolyA+ RNA was extracted and purified from two separate clones of E14, which were treated as biological replicate

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Epigenetic regulation of unique genes and repetitive elements by KRAB zinc finger protein ZFP57 in embryonic stem cells

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

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