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

Elife. 2017 Aug 14:6:e25125. doi: 10.7554/eLife.25125.

Abstract

To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is 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 also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.

Keywords: H3K27ac; XCI escapers; allelic expression; developmental biology; enhancer; evolutionary biology; genomic imprinting; genomics; mouse; stem cells; strain-biased expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Mice
  • Sequence Analysis, RNA
  • X Chromosome Inactivation