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

被引:107
作者
Andergassen, Daniel [1 ,4 ]
Dotter, Christoph P. [1 ,5 ]
Wenzel, Daniel [2 ]
Sigl, Verena [2 ]
Bammer, Philipp C. [1 ,6 ]
Muckenhuber, Markus [1 ,7 ]
Mayer, Daniela [1 ,6 ]
Kulinski, Tomasz M. [1 ,8 ]
Theussl, Hans-Christian [3 ]
Penninger, Josef M. [2 ]
Bock, Christoph [1 ]
Barlow, Denise P. [1 ]
Pauler, Florian M. [1 ,5 ]
Hudson, Quanah J. [1 ,9 ]
机构
[1] Austrian Acad Sci, Res Ctr Mol Med, CeMM, Vienna, Austria
[2] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, Vienna, Austria
[3] Inst Mol Pathol, IMP IMBA Transgen Serv, Vienna, Austria
[4] Harvard Univ, Dept Stem Cell & Regenerat Med, Cambridge, MA 02138 USA
[5] IST Austria, Klosterneuburg, Austria
[6] Friedrich Miescher Inst Biomed Res, Basel, Switzerland
[7] German Canc Res Ctr, Heidelberg, Germany
[8] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland
[9] Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria
基金
奥地利科学基金会;
关键词
X-CHROMOSOME INACTIVATION; IMPRINTED GENE-EXPRESSION; EMBRYONIC STEM-CELLS; RNA-SEQ; MONOALLELIC EXPRESSION; NONCODING RNAS; GENOME; ORIGIN; MICE; IDENTIFICATION;
D O I
10.7554/eLife.25125
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 Fl 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.
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页数:29
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