title: Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch.
abstract: Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here, we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Hdac3 ablation leads to a significant increase of astrocytes with a concomitant loss of oligodendrocytes. Lineage tracing indicates that the ectopic astrocytes originate from oligodendrocyte progenitors. Genome-wide occupancy analysis reveals that Hdac3 interacts with p300 to activate oligodendroglial lineage-specific genes, while suppressing astroglial differentiation genes including NFIA. Furthermore, we find that Hdac3 modulates the acetylation state of Stat3 and competes with Stat3 for p300 binding to antagonize astrogliogenesis. Thus, our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrocyte identity while inhibiting NFIA and Stat3-mediated astrogliogenesis, and thereby regulates phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision.
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Liguo
authors: L
authors: Zhang
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Xuelian
authors: X
authors: He
authors: Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors: Lei
authors: L
authors: Liu
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Minqing
authors: M
authors: Jiang
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Chuntao
authors: C
authors: Zhao
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Haibo
authors: H
authors: Wang
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Molecular Biology and Integrated Biology Program, University of Texas Southwestern Medical Center, Dallas, TX 75239, USA.
authors: Danyang
authors: D
authors: He
authors: Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors: Tao
authors: T
authors: Zheng
authors: Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors: Xianyao
authors: X
authors: Zhou
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Aishlin
authors: A
authors: Hassan
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Zhixing
authors: Z
authors: Ma
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Mei
authors: M
authors: Xin
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Zheng
authors: Z
authors: Sun
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Mitchell A
authors: MA
authors: Lazar
authors: Center for Translational Neuromedicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors: Steven A
authors: SA
authors: Goldman
authors: Department of Molecular Biology and Integrated Biology Program, University of Texas Southwestern Medical Center, Dallas, TX 75239, USA.
authors: Eric N
authors: EN
authors: Olson
authors: Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: richard.lu@cchmc.org.
authors: Q Richard
authors: QR
authors: Lu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050881:E1A-Associated p300 Protein; D006655:Histone Deacetylases; D000099186:Histone Deacetylase 3; C494361:Ep300 protein, mouse