title: Osteocalcin gene expression is regulated by wild-type p53.
abstract: The tumor-suppressor p53 is a transcription factor that regulates a number of genes in the process of cell-cycle inhibition, apoptosis, and DNA damage. Recent studies have revealed a crucial role for p53 in bone remodeling. In our previous studies we have shown that p53 is an important regulator of osteoblast differentiation. In this study we investigated the role of p53 in the regulation of human osteocalcin gene expression. We observed that osteocalcin promoter activity could be upregulated by both exogenous and endogenous p53 and downregulated by p53-specific small interfering RNA. DNA affinity immunoblotting assay showed that p53 can bind to the human osteocalcin promoter in vitro. We further identified a p53 response element within the osteocalcin promoter region using a chromatin immunoprecipitation assay. Furthermore, we observed an additive effect of p53 and VDR on the regulation of osteocalcin promoter activity. Our findings suggest that p53 may directly target the human osteocalcin gene and positively affect osteocalcin gene expression.
authors.affiliation: Department of Biochemistry, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA.
authors.forename: Hankui
authors.initials: H
authors.lastname: Chen
authors.forename: Emily
authors.initials: E
authors.lastname: Hays
authors.forename: Jay
authors.initials: J
authors.lastname: Liboon
authors.forename: Chris
authors.initials: C
authors.lastname: Neely
authors.forename: Kevin
authors.initials: K
authors.lastname: Kolman
authors.forename: Nalini
authors.initials: N
authors.lastname: Chandar
mesh_terms: D000818:Animals; D001483:Base Sequence; D016723:Bone Remodeling / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D015675:Osteocalcin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53; D015675:Osteocalcin