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Cell Rep. 2015 Dec 1;13(9):1842-54. doi: 10.1016/j.celrep.2015.10.046. Epub 2015 Nov 19.

Loss of BAF (mSWI/SNF) Complexes Causes Global Transcriptional and Chromatin State Changes in Forebrain Development.

Author information

  • 1Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
  • 2Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
  • 3Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37077 Goettingen, Germany; German Center for Neurodegenerative Diseases, 37077 Goettingen, Germany.
  • 4Department of Biological Sciences, Institute of Molecular Biology and Genetics, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea.
  • 5Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37077 Goettingen, Germany; German Center for Neurodegenerative Diseases, 37077 Goettingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), 37075 Goettingen, Germany.
  • 6Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), 37075 Goettingen, Germany.
  • 7Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), 37075 Goettingen, Germany.
  • 8Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), 37075 Goettingen, Germany. Electronic address: tran.tuoc@med.uni-goettingen.de.

Abstract

BAF (Brg/Brm-associated factors) complexes play important roles in development and are linked to chromatin plasticity at selected genomic loci. Nevertheless, a full understanding of their role in development and chromatin remodeling has been hindered by the absence of mutants completely lacking BAF complexes. Here, we report that the loss of BAF155/BAF170 in double-conditional knockout (dcKO) mice eliminates all known BAF subunits, resulting in an overall reduction in active chromatin marks (H3K9Ac), a global increase in repressive marks (H3K27me2/3), and downregulation of gene expression. We demonstrate that BAF complexes interact with H3K27 demethylases (JMJD3 and UTX) and potentiate their activity. Importantly, BAF complexes are indispensable for forebrain development, including proliferation, differentiation, and cell survival of neural progenitor cells. Our findings reveal a molecular mechanism mediated by BAF complexes that controls the global transcriptional program and chromatin state in development.

PMID:
26655900
DOI:
10.1016/j.celrep.2015.10.046
[PubMed - indexed for MEDLINE]
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