Loss of maternal Trim28 causes male-predominant early embryonic lethality
- Abhishek Sampath Kumar1,
- Michelle K.Y. Seah1,6,
- Ka Yi Ling1,6,
- Yaju Wang1,
- Joel H.L. Tan1,2,
- Sandra Nitsch1,
- Shu Ly Lim1,
- Chanchao Lorthongpanich3,
- Heike Wollmann4,
- Diana H.P. Low5,
- Ernesto Guccione2,5 and
- Daniel M. Messerschmidt1,2
- 1Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673;
- 2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074;
- 3Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok 10700, Thailand;
- 4Next-Generation Sequencing Unit of DNA Sequencing Facility, IMCB, A*STAR, 138673, Singapore;
- 5Methyltransferases in Development and Disease Group, IMCB, A*STAR, Singapore 138673
- Corresponding author: danielm{at}imcb.a-star.edu.sg
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↵6 These authors contributed equally to this work.
Abstract
Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood. Here we show that the Y-linked gene Rbmy1a1 is highly methylated in mature sperm and resists DNA demethylation post-fertilization. Aberrant hypomethylation of the Rbmy1a1 promoter results in its ectopic activation, causing male-specific peri-implantation lethality. Rbmy1a1 is a novel target of the TRIM28 complex, which is required to protect its repressive epigenetic state during embryonic epigenetic reprogramming.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.291195.116.
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Freely available online through the Genes & Development Open Access option.
- Received October 4, 2016.
- Accepted December 27, 2016.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
