Pluto Bioinformatics

GSE75957: Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression

Bulk RNA sequencing

Allele-specific expression is important in development and disease, but a complete picture is lacking. Therefore, we mapped allelic-specific expression in 23 tissues during mouse development, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. By using rRNA depleted RNA-seq we were able to map allelic expression of lncRNAs that may be lowly expressed or non-polyadenylated. Analysis of this data together with ChIP-seq and genetic models reveals previously unappreciated aspects of the regulation of allelic expression. We demonstrate that allelic expression arising from genetic differences between the alleles, or from the epigenetic processes XCI and genomic imprinting, is surprisingly highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We detect a higher rate of XCI escapers than most previous mouse studies, (10% genes escaping per tissue similar to reports in human), while leg muscle shows an unexpectedly high rate of 50% escapers. By surveying a range of tissues during development, and by performing extensive validation including an embryo transfer experiment to exclude false positives from placental maternal contamination, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This increases the proportion of imprinted genes that are clustered (>90%), and shows that cluster size varies dynamically during development, and can be substantially larger than previously thought, with the Igf2r cluster extending over 10Mb in placenta, making it the largest autosomal cis-regulated region in mammals. SOURCE: Daniel AndergassenBarlow CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences