title: Brg1 directly regulates Olig2 transcription and is required for oligodendrocyte progenitor cell specification.
abstract: The Olig2 basic-helix-loop-helix transcription factor promotes oligodendrocyte specification in early neural progenitor cells (NPCs), including radial glial cells, in part by recruiting SWI/SNF chromatin remodeling complexes to the enhancers of genes involved in oligodendrocyte differentiation. How Olig2 expression is regulated during oligodendrogliogenesis is not clear. Here, we find that the Brg1 subunit of SWI/SNF complexes interacts with a proximal Olig2 promoter and represses Olig2 transcription in the mouse cortex at E14, when oligodendrocyte progenitors (OPCs) are not yet found in this location. Brg1 does not interact with the Olig2 promoter in the E14 ganglionic eminence, where NPCs differentiate into Olig2-positive OPCs. Consistent with these findings, Brg1-null NPCs demonstrate precocious expression of Olig2 in the cortex. However, these cells fail to differentiate into OPCs. We further find that Brg1 is necessary for neuroepithelial-to-radial glial cell transition, but not neuronal differentiation despite a reduction in expression of the pro-neural transcription factor Pax6. Collectively, these and earlier findings support a model whereby Brg1 promotes neurogenic radial glial progenitor cell specification but is dispensable for neuronal differentiation. Concurrently, Brg1 represses Olig2 expression and the specification of OPCs, but is required for OPC differentiation and oligodendrocyte maturation.
authors.affiliation: Integrative Biosciences Department, School of Dentistry, Oregon Health & Science University, Portland, OR 97239, USA; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Banine
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Feistel
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Foster
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Rubing
authors.initials: R
authors.lastname: Xing
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Struve
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA; Department of Cell, Developmental and Cancer Biology, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: shermanl@ohsu.edu.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D004265:DNA Helicases / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology*; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004265:DNA Helicases; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D014157:Transcription Factors; C512773:Olig2 protein, mouse; C513194:Smarca4 protein, mouse
keywords: Brg1; Olig2; Oligodendrocyte progenitors; Pax6; Radial glia