title: The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.
abstract: Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination.
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Laitman
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Linnéa
authors.initials: L
authors.lastname: Asp
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: John N
authors.initials: JN
authors.lastname: Mariani
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Setsu
authors.initials: S
authors.lastname: Sawai
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Candice
authors.initials: C
authors.lastname: Chapouly
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Sam
authors.initials: S
authors.lastname: Horng
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Kramer
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Nesanet
authors.initials: N
authors.lastname: Mitiku
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Loo
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Natalie
authors.initials: N
authors.lastname: Burlant
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Xiomara
authors.identifier: 0000-0002-3024-3826
authors.initials: X
authors.lastname: Pedre
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Yuko
authors.identifier: 0000-0001-5828-442X
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: German
authors.initials: G
authors.lastname: Nudelman
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Elena
authors.identifier: 0000-0002-4828-7771
authors.initials: E
authors.lastname: Zaslavsky
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Braun
authors.affiliation: Pediatrics, Cincinnati Childrens' Hospital, Cincinnati, Ohio, United States of America.
authors.forename: Q Richard
authors.initials: QR
authors.lastname: Lu
authors.affiliation: School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Goutham
authors.initials: G
authors.lastname: Narla
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Raine
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casaccia
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: John
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism
chemical_list: D002843:Chromatin; C494200:Il6st protein, mouse; C527077:KPNA1 protein, mouse; C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D028901:alpha Karyopherins; D050822:Cytokine Receptor gp130