title: BMP-induced REST regulates the establishment and maintenance of astrocytic identity.
abstract: Once they have differentiated, cells retain their individual character and repress genes that are specifically expressed in other cell lineages, but how alternative fate choice is restricted during and/or after differentiation remains unclear. In the mammalian central nervous system, neurons, astrocytes, and oligodendrocytes are generated throughout life from common tripotent neural progenitor cells (NPCs). Bone morphogenetic proteins (BMPs) are well-known astrocyte-inducing cytokines. We show here that the expression of a transcriptional repressor, RE1 silencer of transcription (REST)/neuron-restrictive silencer factor (NRSF), is up-regulated and sustained by BMP signal activation in the course of astrocytic differentiation of NPCs, and restricts neuronal differentiation. We further show that, in differentiated astrocytes, endogenous REST/NRSF associates with various neuronal genes and that disruption of its function resulted in their derepression, thereby explaining how ectopic neuronal gene expression is prevented in cells with astrocytic traits. Collectively, our results suggest that REST/NRSF functions as a molecular regulator of the nonneuronal phenotype in astrocytes.
authors.affiliation: Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0101, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kohyama
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sanosaka
authors.forename: Akinori
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Eriko
authors.initials: E
authors.lastname: Takatsuka
authors.forename: Keita
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Kinichi
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D000099229:RE1-Silencing Transcription Factor
chemical_list: D019485:Bone Morphogenetic Proteins; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor