title: Loss of BAF (mSWI/SNF) Complexes Causes Global Transcriptional and Chromatin State Changes in Forebrain Development.
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.
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Narayanan
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Pirouz
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, 37077 Goettingen, Germany; German Center for Neurodegenerative Diseases, 37077 Goettingen, Germany.
authors.forename: Cemil
authors.initials: C
authors.lastname: Kerimoglu
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
authors.forename: Linh
authors.initials: L
authors.lastname: Pham
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Wagener
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
authors.forename: Kamila A
authors.initials: KA
authors.lastname: Kiszka
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August-University Goettingen, 37075 Goettingen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rosenbusch
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology and Genetics, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea.
authors.forename: Rho H
authors.initials: RH
authors.lastname: Seong
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kessel
authors.affiliation: Department 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.
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), 37075 Goettingen, Germany.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Stoykova
authors.affiliation: Institute 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.
authors.forename: Jochen F
authors.initials: JF
authors.lastname: Staiger
authors.affiliation: Institute 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.
authors.forename: Tran
authors.initials: T
authors.lastname: Tuoc
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C491090:Smarcc1 protein, mouse; C587872:Smarcc2 protein, mouse; D014157:Transcription Factors; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse; C513194:Smarca4 protein, mouse; D004265:DNA Helicases