Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally

  1. Jadiel A Wasson
  2. Ashley K Simon
  3. Dexter A Myrick
  4. Gernot Wolf
  5. Shawn Driscoll
  6. Samuel L Pfaff
  7. Todd S Macfarlan
  8. David J Katz  Is a corresponding author
  1. Emory University School of Medicine, United States
  2. National Institutes of health, United States
  3. 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

  1. Jadiel A Wasson

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ashley K Simon

    Department of Human Genetics, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dexter A Myrick

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Gernot Wolf

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shawn Driscoll

    Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Samuel L Pfaff

    Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Todd S Macfarlan

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. David J Katz

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    For correspondence
    djkatz@emory.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All mouse work was performed under the approved guidelines of the Emory University IACUC (protocol #2002534).

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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  1. Jadiel A Wasson
  2. Ashley K Simon
  3. Dexter A Myrick
  4. Gernot Wolf
  5. Shawn Driscoll
  6. Samuel L Pfaff
  7. Todd S Macfarlan
  8. David J Katz
(2016)
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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https://doi.org/10.7554/eLife.08848