Conversion of random X-inactivation to imprinted X-inactivation by maternal PRC2

Abstract
Data availability
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Abstract

Imprinted X-inactivation silences genes exclusively on the paternally-inherited X-chromosome and is a paradigm of transgenerational epigenetic inheritance in mammals. Here, we test the role of maternal vs. zygotic Polycomb repressive complex 2 (PRC2) protein EED in orchestrating imprinted X-inactivation in mouse embryos. In maternal-null (Eed^m-/-) but not zygotic-null (Eed^-/-) early embryos, the maternal X-chromosome ectopically induced Xist and underwent inactivation. Eed^m-/- females subsequently stochastically silenced Xist from one of the two X-chromosomes and displayed random X-inactivation. This effect was exacerbated in embryos lacking both maternal and zygotic EED (Eed^mz-/-), suggesting that zygotic EED can also contribute to the onset of imprinted X-inactivation. Xist expression dynamics in Eed^m-/- embryos resemble that of early human embryos, which lack oocyte-derived maternal PRC2 and only undergo random X-inactivation. Thus, expression of PRC2 in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals.

Data availability

Sequencing data have been deposited in GEO under accession number GSE123173. The analyzed sequencing data are also included as Supplementary File 3.

The following data sets were generated

1. Harris C
2. Cloutier M
3. Trotter M
4. Hinten M
5. Gayen S
6. Kalantry S
(2018) Conversion of Random X-inactivation to Imprinted X-inactivation by Maternal PRC2
NCBI Gene Expression Omnibus, GSE123173.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123173

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NCBI BioProject, PRJNA146903.

https://www.ncbi.nlm.nih.gov/pubmed/21953461
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(2015) Gene expression during the first three days of human development
NCBI BioProject, PRJEB8994.

https://www.ncbi.nlm.nih.gov/bioproject/PRJEB8994
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https://www.nature.com/articles/nature11244

Article and author information

Author details

Clair Harris

Department of Human Genetics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Marissa Cloutier

Department of Human Genetics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Megan Trotter

Department of Human Genetics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Michael Hinten

Department of Human Genetics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Srimonta Gayen

Department of Human Genetics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Zhenhai Du

Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Wei Xie

Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Sundeep Kalantry

Department of Human Genetics, University of Michigan, Ann Arbor, United States

For correspondence
kalantry@umich.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0763-8050

Funding

NIH Office of the Director (DP2-OD-008646)

Sundeep Kalantry

National Institutes of Health (R01GM124571)

Sundeep Kalantry

National Institutes of Health (R01HD095463)

Sundeep Kalantry

National Institute of General Medical Sciences (T32GM07544)

Marissa Cloutier
Megan Trotter

March of Dimes Foundation (5-FY12-119)

Sundeep Kalantry

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to protocols approved by the University Committee on Use and Care of Animals (UCUCA) at the University of Michigan (protocol #s PRO6455 and PRO8425).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.