title: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
abstract: Oligodendrocyte development is regulated by the interaction of repressors and activators in a complex transcriptional network. We found that two histone-modifying enzymes, HDAC1 and HDAC2, were required for oligodendrocyte formation. Genetic deletion of both Hdac1 and Hdac2 in oligodendrocyte lineage cells resulted in stabilization and nuclear translocation of beta-catenin, which negatively regulates oligodendrocyte development by repressing Olig2 expression. We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of beta-catenin for regulating oligodendrocyte differentiation. Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte maturation, whereas expression of its dominant-repressive form promoted precocious oligodendrocyte specification in developing chick neural tube. Transcriptional co-repressors HDAC1 and HDAC2 compete with beta-catenin for TCF7L2 interaction to regulate downstream genes involved in oligodendrocyte differentiation. Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation.
authors.affiliation: Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: ThaoNguyen
authors.initials: T
authors.lastname: Hoang
authors.forename: Rusty L
authors.initials: RL
authors.lastname: Montgomery
authors.forename: Xian-hui
authors.initials: XH
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.forename: Tom
authors.initials: T
authors.lastname: Hu
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Jenny
authors.initials: J
authors.lastname: Hsieh
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Q Richard
authors.initials: QR
authors.lastname: Lu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D005260:Female; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000502:physiology; D051820:TCF Transcription Factors / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; C553059:Tcf7l2 protein, rat; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins; D051176:beta Catenin; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; C533426:Hdac2 protein, rat; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases