Transcriptional induction of the osteocalcin gene during osteoblast differentiation involves acetylation of histones h3 and h4
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Medical Subject Headings
Acetylation; Alkaline Phosphatase; Amino Acid Sequence; Animals; Bone Neoplasms; Cell Differentiation; Cells, Cultured; Cholecalciferol; Chromatin; Core Binding Factor Alpha 1 Subunit; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Gene Expression Regulation; Histones; Molecular Sequence Data; *Neoplasm Proteins; Osteoblasts; Osteocalcin; Osteopontin; Osteosarcoma; Promoter Regions (Genetics); Rats; Sialoglycoproteins; Transcription Factors; *Transcription, Genetic
Life Sciences | Medicine and Health Sciences
The remodeling of chromatin is required for tissue-specific gene activation to permit interactions of transcription factors and coregulators with their cognate elements. Here, we investigate the chromatin-mediated mechanisms by which the bone-specific osteocalcin (OC) gene is transcriptionally activated during cessation of cell growth in ROS 17/2.8 osteosarcoma cells and during normal osteoblast differentiation. Acetylation of histones H3 and H4 at the OC gene promoter was assayed during the proliferative and postproliferative stages of cell growth by using chromatin immunoprecipitation assays with antibodies that recognize different acetylated forms of histones H3 or H4. The results show that the promoter and coding regions of the OC gene contain very low levels of acetylated histones H3 and H4 during the proliferative period of osteoblast differentiation when the OC gene is inactive. Active expression of the OC gene in mature osteoblasts and confluent ROS 17/2.8 cells is functionally linked to preferential acetylation of histone H4 and, to a lesser extent, to acetylation of histone H3. Histone acetylation at the loci for RUNX2 (CBFA1), alkaline phosphatase, bone sialoprotein, osteopontin, and the cell growth regulator p21, which are expressed throughout osteoblast differentiation, is not altered postproliferatively. We conclude that acetylation of histones H3 and H4 is functionally coupled to the chromatin remodeling events that mediate the developmental induction of OC gene transcription in bone cells.
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Citation: Mol Endocrinol. 2003 Apr;17(4):743-56. Epub 2003 Jan 9. Link to article on publisher's site