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Allelome.PRO A pipeline to define allele-specific genome features

ABSTRACT: We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results.

ORGANISM(S): Mus musculus

PROVIDER: GSE69168 | GEO | 2015/08/03

SECONDARY ACCESSION(S): PRJNA284740

REPOSITORIES: GEO

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Allelome.PRO A pipeline to define allele-specific genome features

Project description:We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. Defining allele-specific genome features from F1 E12.5 mouse embryonic fibroblasts

2015-08-03 | E-GEOD-69168 | biostudies-arrayexpress

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Project description:Multiple regulatory layers influence allele-specific expression (ASE), particularly through sequence-dependent and parent-of-origin-dependent mechanisms at the transcriptional level. However, little is known about allele-specific gene regulation at the post-transcriptional level. Here, we conduct transcriptome-wide analysis of allele-specific m6A in mice. Using early postnatal cerebellum and cerebrum samples from reciprocal crosses of two divergent mouse strains, we employed quantitative m6A assays to measure allelic differences in m6A at single-base resolution. Our study reveals widespread sequence-dependent allelic imbalance in m6A methylation, identifying thousands of allele-specific m6A (ASm6A) sites with statistically significant and reproducible allelic methylation differences across diverse samples. We find evidence of potential cis-regulatory variants within 50-nt flanking regions of these ASm6A sites, with the highest enrichment at the motif positions. Intriguingly, we detect parental effects on allelic methylation across m6A sites exhibiting parent-of-origin-dependent ASE. For both sequence- and parent-of-origin-dependent allelic m6A methylation, we observe opposing allelic preferences between methylation and expression, suggesting a potential role of ASm6A in regulating ASE through negative effects on gene expression. Overall, our findings reveal that both cis-acting and parent-of-origin effects influence ASm6A, offering new insights into post-transcriptional mechanisms of ASE regulation.

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Sequence and parent-of-origin dependent m6A contribute to allele-specific gene expression [m6A-seq]

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Genomic DNA mixture series in Allele Specific Expression study

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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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Genomic DNA mixture series in Allele Specific Expression study

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