title: Chromatin regulation by BAF170 controls cerebral cortical size and thickness.
abstract: Increased cortical size is essential to the enhanced intellectual capacity of primates during mammalian evolution. The mechanisms that control cortical size are largely unknown. Here, we show that mammalian BAF170, a subunit of the chromatin remodeling complex mSWI/SNF, is an intrinsic factor that controls cortical size. We find that conditional deletion of BAF170 promotes indirect neurogenesis by increasing the pool of intermediate progenitors (IPs) and results in an enlarged cortex, whereas cortex-specific BAF170 overexpression results in the opposite phenotype. Mechanistically, BAF170 competes with BAF155 subunit in the BAF complex, affecting euchromatin structure and thereby modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors. Our findings reveal a molecular mechanism mediated by the mSWI/SNF chromatin-remodeling complex that controls cortical architecture.
authors: Research Group of Molecular Developmental Neurobiology, Department of Molecular Cell Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors: Tran Cong
authors: TC
authors: Tuoc
authors: Susann
authors: S
authors: Boretius
authors: Stephen N
authors: SN
authors: Sansom
authors: Mara-Elena
authors: ME
authors: Pitulescu
authors: Jens
authors: J
authors: Frahm
authors: Frederick J
authors: FJ
authors: Livesey
authors: Anastassia
authors: A
authors: Stoykova
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002843:Chromatin; D005136:Eye Proteins; D006657:Histones; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C000624101:Cux1 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C491090:Smarcc1 protein, mouse