title: Structural insights into histone demethylase NO66 in interaction with osteoblast-specific transcription factor osterix and gene repression.
abstract: Osterix (Osx) is an osteoblast-specific transcriptional factor and is required for osteoblast differentiation and bone formation. A JmjC domain-containing protein NO66 was previously found to participate in regulation of Osx transcriptional activity and plays an important role in osteoblast differentiation through interaction with Osx. Here, we report the crystal structure of NO66 forming in a functional tetramer. A hinge domain links the N-terminal JmjC domain and C-terminal winged helix-turn-helix domain of NO66, and both domains are essential for tetrameric assembly. The oligomerization interface of NO66 interacts with a conserved fragment of Osx. We show that the hinge domain-dependent oligomerization of NO66 is essential for inhibition of Osx-dependent gene activation. Our findings suggest that homo-oligomerization of JmjC domain containing proteins might play a physiological role through interactions with other regulatory factors during gene expression.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Yin
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Departments of Genetics, Houston, Texas.
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.affiliation: Endocrine Neoplasia and Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: ksinha@mdanderson.org.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Sinha
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230027, China. Electronic address: zangjy@ustc.edu.cn.
authors.forename: Jianye
authors.initials: J
authors.lastname: Zang
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D049308:Dioxygenases; D005786:Gene Expression Regulation / Q000502:physiology*; D019077:Helix-Turn-Helix Motifs; D056466:Histone Demethylases; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D012097:Repressor Proteins; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D049308:Dioxygenases; D056466:Histone Demethylases; C492859:RIOX1 protein, human
keywords: Bone; Gene Regulation; General Transcription Factors; Histone Modification; Osteoblasts; Protein Structure