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

Author:

Andergassen Daniel1ORCID,Dotter Christoph P1,Wenzel Daniel2,Sigl Verena2,Bammer Philipp C1,Muckenhuber Markus1,Mayer Daniela1,Kulinski Tomasz M1,Theussl Hans-Christian3,Penninger Josef M2ORCID,Bock Christoph1ORCID,Barlow Denise P1,Pauler Florian M1,Hudson Quanah J1ORCID

Affiliation:

1. CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

2. IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria

3. IMP/IMBA Transgenic Service, Institute of Molecular Pathology, Vienna, Austria

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.

Funder

Austrian Science Fund

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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