title: HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination.
abstract: Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, but the molecular mechanisms underlying such a process are poorly understood. We found that the acetylation state of NF-κB, which is regulated by histone deacetylases (HDACs) 1 and 2, is critical for orchestrating the myelination program. Mice lacking both HDACs 1 and 2 (HDAC1/2) exhibited severe myelin deficiency with Schwann cell development arrested at the immature stage. NF-κB p65 became heavily acetylated in HDAC1/2 mutants, inhibiting the expression of positive regulators of myelination and inducing the expression of differentiation inhibitors. We observed that the NF-κB protein complex switched from associating with p300 to associating with HDAC1/2 as Schwann cells differentiated. NF-κB and HDAC1/2 acted in a coordinated fashion to regulate the transcriptionally linked chromatin state for Schwann cell myelination. Thus, our results reveal an HDAC-mediated developmental switch for controlling myelination in the peripheral nervous system.
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, Texas, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Sung Ok
authors.initials: SO
authors.lastname: Yoon
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xu
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.forename: John
authors.initials: J
authors.lastname: Svaren
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Nave
authors.forename: Haesun A
authors.initials: HA
authors.lastname: Kim
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Q Richard
authors.initials: QR
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000502:physiology*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D012583:Schwann Cells / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D002843:Chromatin; D016328:NF-kappa B; D051996:Transcription Factor RelA; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2