Conversion of random X-inactivation to imprinted X-inactivation by maternal PRC2
- University of Michigan, United States
- Tsinghua University, China
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 (Eedm-/-) but not zygotic-null (Eed-/-) early embryos, the maternal X-chromosome ectopically induced Xist and underwent inactivation. Eedm-/- 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 (Eedmz-/-), suggesting that zygotic EED can also contribute to the onset of imprinted X-inactivation. Xist expression dynamics in Eedm-/- 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.
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Conversion of Random X-inactivation to Imprinted X-inactivation by Maternal PRC2NCBI Gene Expression Omnibus, GSE123173.
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The transcriptome of a human polar body accurately reflects its sibling oocyteNCBI BioProject, PRJNA146903.
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Gene expression during the first three days of human developmentNCBI BioProject, PRJEB8994.
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Embryonic stem cell potency fluctuates with endogenous retrovirus activity.NCBI BioProject, PRJNA154207.
Article and author information
Author details
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
© 2019, Harris et al.
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.
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Conversion of random X-inactivation to imprinted X-inactivation by maternal PRC2
eLife 8:e44258.
https://doi.org/10.7554/eLife.44258
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