Loss of BAF (mSWI/SNF) Complexes Causes Global Transcriptional and Chromatin State Changes in Forebrain Development
Ramanathan Narayanan,
Mehdi Pirouz,
Cemil Kerimoglu,
Linh Pham,
Robin J. Wagener,
Kamila A. Kiszka,
Joachim Rosenbusch,
Rho H. Seong,
Michael Kessel,
Andre Fischer,
Anastassia Stoykova,
Jochen F. Staiger,
Tran Tuoc
Affiliations
Ramanathan Narayanan
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Mehdi Pirouz
Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany
Cemil Kerimoglu
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37077 Goettingen, Germany
Linh Pham
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Robin J. Wagener
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Kamila A. Kiszka
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Joachim Rosenbusch
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Rho H. Seong
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea
Michael Kessel
Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany
Andre Fischer
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37077 Goettingen, Germany
Anastassia Stoykova
Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany
Jochen F. Staiger
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
Tran Tuoc
Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany
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.
