Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally
- Emory University School of Medicine, United States
- National Institutes of health, United States
- Howard Hughes Medical Institute, The Salk Institute for Biological Studies, United States
Abstract
Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.
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Author details
Ethics
Animal experimentation: All mouse work was performed under the approved guidelines of the Emory University IACUC (protocol #2002534).
Reviewing Editor
- Anne C Ferguson-Smith, University of Cambridge, United Kingdom
Version history
- Received: May 21, 2015
- Accepted: January 25, 2016
- Accepted Manuscript published: January 27, 2016 (version 1)
- Version of Record published: April 5, 2016 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally
eLife 5:e08848.
https://doi.org/10.7554/eLife.08848
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