title: Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation.
abstract: Osteogenesis is a complex process associated with dramatic changes in gene expression. To elucidate whether modifications in chromatin structure are involved in osteoblast differentiation, we examined the expression levels of histone deacetylases (HDACs) and the degree of histone acetylation at the promoter regions of osteogenic genes. During osteogenesis, total HDAC enzymatic activity was decreased with significant reduction in HDAC1 expression. Consistently, recruitment of HDAC1 to the promoters of osteoblast marker genes, including osterix and osteocalcin, was down-regulated, whereas histone H3 and H4 were hyperacetylated at those promoters during osteoblast differentiation. Moreover, suppression of HDAC activity with a HDAC inhibitor, sodium butyrate, accelerated osteogenesis by inducing osteoblast marker genes including osteopontin and alkaline phosphatase. Consistently, knockdown of HDAC1 by the short interference RNA system stimulated osteoblast differentiation. Taken together, these data propose that down-regulation of HDAC1 is an important process for osteogenesis.
authors.affiliation: Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul, Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: A Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: So Yun
authors.initials: SY
authors.lastname: Park
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002087:Butyrates; D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D034741:RNA, Small Interfering; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D015675:Osteocalcin; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases