Postproliferative transcription of the rat osteocalcin gene is reflected by vitamin D-responsive developmental modifications in protein-DNA interactions at basal and enhancer promoter elements
Department of Cell Biology; Department of Medicine, Division of Diabetes
Animals; Base Sequence; Cell Division; Cells, Cultured; DNA; DNA-Binding Proteins; Dexamethasone; *Enhancer Elements (Genetics); Humans; Molecular Sequence Data; Nuclear Proteins; Oligodeoxyribonucleotides; Osteoblasts; Osteocalcin; Phenotype; *Promoter Regions (Genetics); Proto-Oncogene Proteins c-jun; Rats; Receptors, Calcitriol; Receptors, Steroid; TATA Box; *Transcription, Genetic; Vitamin D
Life Sciences | Medicine and Health Sciences
In the osteocalcin (OC) gene promoter, both independent positive and negative regulatory elements, as well as others with contiguous [TATA/glucocorticoid-responsive elements (GRE)] or overlapping [TATA/GRE, vitamin D-responsive enhancer elements (VDRE)/AP-1, and OC box/AP-1] domains, are sites for modifications in protein-DNA interactions. In the present studies, we have examined nuclear protein extracts from fetal rat calvarial cells that undergo a developmental sequence of bone cell differentiation. Our results demonstrate modifications in protein-DNA interactions that relate to the developmental stages of the osteoblast and support developmental regulation of OC gene transcription. Basal expression of the OC gene is associated with sequence-specific protein-DNA interactions at the OC box, VDRE, and TATA/GRE box. Distinct differences are observed in proliferating osteoblasts, where the OC gene is not transcribed compared to postproliferative, differentiated osteoblasts that transcribe the OC gene. Furthermore, the protein-DNA complexes that reflect hormonal control are also developmentally regulated, mediating both the transcriptionally active and repressed states of the OC gene. For example, in proliferating osteoblasts, a vitamin D receptor-antibody-sensitive complex is formed that is different from the DNA binding complex induced by vitamin D postproliferatively when the OC gene is transcribed. Mutational analysis of the steroid hormone binding domain and the overlapping AP-1 site at the VDRE supports mutually exclusive occupancy by Fos-Jun heterodimers and vitamin D receptor. Such protein-DNA interactions at the VDRE are consistent with repression of competency for vitamin D-mediated transcriptional enhancement in proliferating osteoblasts expressing high levels of Fos and Jun.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1503-7.
Proceedings of the National Academy of Sciences of the United States of America
Owen TA, Bortell R, Shalhoub V, Heinrichs A, Stein JL, Stein GS, Lian JB. (1993). Postproliferative transcription of the rat osteocalcin gene is reflected by vitamin D-responsive developmental modifications in protein-DNA interactions at basal and enhancer promoter elements. Open Access Publications by UMMS Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/1817