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A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes.

S Bultman1, T Gebuhr, D Yee

  • 1Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.

Molecular Cell
|February 13, 2001
PubMed
Summary

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Brahma-related gene 1 (Brg1) is essential for early mammalian development, as Brg1 null mutations cause embryonic lethality. This challenges the idea of functional redundancy in SWI/SNF chromatin remodelers.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Mammalian SWI/SNF complexes are ATP-dependent chromatin remodelers.
  • These complexes use either Brahma (Brm) or Brahma-related gene 1 (Brg1) catalytic subunits.
  • Brm's dispensability suggested functional redundancy between Brm and Brg1.

Purpose of the Study:

  • To investigate the functional necessity of Brg1 in mammalian development.
  • To test the hypothesis of functional redundancy between Brm and Brg1.

Main Methods:

  • Gene targeting to create a Brg1 null mutation in mice.
  • Analysis of homozygous and heterozygous Brg1 mutant embryos.
  • Blastocyst outgrowth studies to assess cell survival.

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Main Results:

  • Brg1 homozygous null mutants exhibit lethality during the periimplantation stage.
  • Neither inner cell mass nor trophectoderm survived in Brg1 null blastocysts.
  • Brg1 heterozygotes showed predispositions to exencephaly and tumors.
  • Brg1 was determined not to be a general cell survival factor.

Conclusions:

  • Biochemically similar SWI/SNF complexes have distinct developmental roles.
  • Brg1 plays a critical, non-redundant role in early mammalian embryogenesis.
  • Loss of Brg1 function has severe developmental consequences, including embryonic lethality and predisposition to specific birth defects and cancers.