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Series GSE55382 Query DataSets for GSE55382
Status Public on May 08, 2015
Title Allele-specific binding of ZFP57 in the regulation of imprinted and mono-allelic expression
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design Input and Zfp57 CHiP-Seq profiles of hybrid Black6/Cast ES cells were generated by sequencing using the Illumina GAIIx platform.
Contributor(s) Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwan K, Sun B, Pederson R, Ferguson-Smith AC
Citation(s) 26025256
Submission date Feb 26, 2014
Last update date May 15, 2019
Contact name Felix Krueger
Organization name The Babraham Institute
Department Bioinformatics
Street address Babraham Hall
City Cambridge
ZIP/Postal code CB22 3AT
Country United Kingdom
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (4)
GSM1335222 s_2_BC8_Zfp57.fastq.gz
GSM1335223 s_3_CB9_Zfp57.fastq.gz
GSM1335224 s_4_BC8_input.fastq.gz
BioProject PRJNA239448
SRA SRP038975

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55382_ZFP57_binding_sites.txt.gz 6.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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