title: HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells.
abstract: Histone deacetylases (HDACs) are major epigenetic regulators. We show that HDAC1 and HDAC2 functions are critical for myelination of the peripheral nervous system. Using mouse genetics, we have ablated Hdac1 and Hdac2 specifically in Schwann cells, resulting in massive Schwann cell loss and virtual absence of myelin in mutant sciatic nerves. Expression of Sox10 and Krox20, the main transcriptional regulators of Schwann cell myelination, was greatly reduced. We demonstrate that in Schwann cells, HDAC1 and HDAC2 exert specific primary functions: HDAC2 activates the transcriptional program of myelination in synergy with Sox10, whereas HDAC1 controls Schwann cell survival by regulating the levels of active β-catenin.
authors.affiliation: Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland. claire.jacob@cell.biol.ethz.ch
authors.forename: Claire
authors.initials: C
authors.lastname: Jacob
authors.forename: Carlos N
authors.initials: CN
authors.lastname: Christen
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Pereira
authors.forename: Christian
authors.initials: C
authors.lastname: Somandin
authors.forename: Arianna
authors.initials: A
authors.lastname: Baggiolini
authors.forename: Pirmin
authors.initials: P
authors.lastname: Lötscher
authors.forename: Murat
authors.initials: M
authors.lastname: Ozçelik
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tricaud
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: Teppei
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000502:physiology; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012583:Schwann Cells / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000201:enzymology* / Q000254:growth & development* / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: C495267:CTNNB1 protein, mouse; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D051176:beta Catenin; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2