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Author Notes:

For correspondence: todd.macfarlan@nih.gov (TSM); djkatz@emory.edu (DJK)

JAW, TSM, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article

AKS, Conception and design, Acquisition of data, Analysis and interpretation of data

DAM, GW, Acquisition of data

SD, Analysis and interpretation of data

SLP, Conception and design, Analysis and interpretation of data

DJK, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article, Contributed unpublished essential data or reagents

See full article for acknowledgements.

The authors declare that no competing interests exist.

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

Subjects:

Research Funding:

J.A.W was supported by the Biochemistry, Cell and Molecular Biology Training Grant (5T32GM008367) and D.A.M by the Emory PREP Post-Bac Program (5R25GM089615-04).

The work was supported by a grant to D.J.K from the National Science Foundation (IOS1354998).

T.S.M. is supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development DIR grant HD008933.

Keywords:

  • KDM1a
  • LSD1
  • MZT
  • developmental biology
  • epigenetics
  • genomic imprinting
  • maternal effect
  • mouse
  • stem cells

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

Tools:

Journal Title:

eLife

Volume:

Volume 5

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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