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Related Concept Videos

Gastrulation01:56

Gastrulation

Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata will form...

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Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
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Distinct roles of DMAP1 in mouse development.

K Naga Mohan1, Feng Ding, J Richard Chaillet

  • 1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA.

Molecular and Cellular Biology
|March 9, 2011
PubMed
Summary

DNMT1-associated protein 1 (DMAP1) is crucial for embryonic development, interacting with both somatic (DNMT1s) and oocyte (DNMT1o) forms of DNA methyltransferase 1. DMAP1 loss causes embryonic lethality, highlighting its role in epigenetic reprogramming.

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Area of Science:

  • Epigenetics
  • Developmental Biology
  • Molecular Biology

Background:

  • DNMT1-associated protein 1 (DMAP1) is part of the TIP60-p400 complex, vital for embryonic stem cell pluripotency.
  • DMAP1 interacts with the somatic form of DNA methyltransferase 1 (DNMT1s), but not the oocyte form (DNMT1o) via a specific domain.
  • The role of DMAP1 in embryonic development, particularly its interaction with different DNMT1 forms, requires further investigation.

Purpose of the Study:

  • To investigate the developmental role of DMAP1 by generating a Dmap1-null allele.
  • To elucidate the distinct functions of DMAP1 in conjunction with DNMT1s and DNMT1o during embryogenesis.
  • To understand DMAP1's contribution to epigenetic reprogramming, including nucleosome remodeling and DNA methylation maintenance.

Main Methods:

  • Generation of a Dmap1-null mouse model.
  • Analysis of embryonic lethality and phenotypes in different Dnmt1 genetic backgrounds (Dnmt1(+/+) and Dnmt1(V)(/)(V)).
  • Detection of DMAP1-DNMT1o complexes in embryonic stem cells under varying expression conditions.

Main Results:

  • Dmap1(-/-) mice exhibited embryonic lethality during preimplantation, irrespective of the Dnmt1 background.
  • In the Dnmt1(V)(/)(V) background, Dmap1(+/-) heterozygotes showed reduced viability and midgestation lethality in Dmap1(+/+) progeny.
  • Loss of Dmap1 in the Dnmt1(V)(/)(V) background led to DNA hypomethylation of imprinted genes, indicating DMAP1's role in DNMT1o-mediated maintenance methylation.
  • A stable DMAP1-DNMT1o complex was observed in ES cells with stable DNMT1o expression, suggesting a novel interaction.

Conclusions:

  • DMAP1-DNMT1s and DMAP1-DNMT1o interactions are essential for mammalian development.
  • DMAP1 plays a critical role in preimplantation epigenetic reprogramming, mediating both TIP60-p400 complex-dependent nucleosome remodeling and DNMT1o-dependent DNA methylation maintenance.
  • The formation of DMAP1-DNMT1o complexes is not readily achieved in the early embryo, implying specific temporal and spatial regulation of these interactions.