The Runx2 transcription factor plays a key role in the 1alpha,25-dihydroxy Vitamin D3-dependent upregulation of the rat osteocalcin (OC) gene expression in osteoblastic cells.
Bone-specific transcription of the osteocalcin (OC) gene is principally regulated by the Runx2 transcription factor and further stimulated in response to 1alpha,25-dihydroxy Vitamin D3 via its specific receptor (VDR). The rat OC gene promoter contains three recognition sites for Runx2 (sites A-C). Mutation of sites A and B, which flank the 1alpha,25-dihydroxy Vitamin D3-responsive element (VDRE), abolishes 1alpha,25-dihydroxy Vitamin D3-dependent enhancement of OC transcription, indicating a tight functional relationship between VDR and Runx2 factors. Additionally, the transcriptional co-activator p300 is recruited to the OC promoter by Runx2 where it up-regulates both basal and 1alpha,25-dihydroxy Vitamin D3-enhanced OC expression. Here, we present an overview of how in osteoblastic cells expressing OC, Runx2 modulates the 1alpha,25-dihydroxy Vitamin D3-dependent stimulation of the OC promoter by first recruiting transcriptional co-activators and then by further stabilizing the interaction of the VDR with the VDRE.
Paredes
Roberto
R
Departamento de Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile.
Arriagada
Gloria
G
Cruzat
Fernando
F
Olate
Juan
J
Van Wijnen
Andre
A
Lian
Jane
J
Stein
Gary
G
Stein
Janet
J
Montecino
Martin
M
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors; D015675:Osteocalcin; D002117:Calcitriol