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CCAAT/enhancer-binding protein delta activates the Runx2-mediated transcription of mouse osteocalcin II promoter

Cited 14 time in Web of Science Cited 14 time in Scopus
Authors
Shin, Chan Soo; Jeon, Min Jae; Yang, Jae-Yeon; Her, Sun-Ju; Kim, Dohee; Kim, Sang Wan; Kim, Seong Yeon
Issue Date
2006
Publisher
Society for Endocrinology
Citation
Journal of Molecular Endocrinology 36 531-546
Keywords
3T3 CellsAnimalsBase SequenceCCAAT-Enhancer-Binding Protein-beta/genetics/metabolismCCAAT-Enhancer-Binding Protein-delta/genetics/*metabolismCells, CulturedCore Binding Factor Alpha 1 Subunit/genetics/*metabolism*Gene Expression RegulationGenes, ReporterMiceMolecular Sequence DataOsteoblasts/cytology/physiologyOsteocalcin/*genetics/metabolism*Promoter Regions, GeneticProtein Isoforms/*genetics/metabolismSequence Alignment*Transcription, Genetic
Abstract
CCAAT/enhancer-binding proteins (C/EBPs) are involved in the regulation of cell proliferation, differentiation, and control of metabolic function. Although the roles of C/EBPs in osteoblasts are largely unknown, both C/EBPbeta and -delta have been shown to enhance rat osteocalcin promoter activity through the synergistic activation of Runx2 at the C/EBP element. Here we show that in the mouse, C/EBPdelta increases the expression of osteocalcin whereas C/EBPbeta does not. This increased expression was found to occur at the transcriptional level, as demonstrated by the increased transcriptional activity from mouse osteocalcin II (OG2) promoter by C/EBPdelta. Although we found three putative C/EBP sites in the -637/+/-34 region of the OG2 promoter, none of these sites showed binding activity with in vitro translated C/EBP proteins. Notably, we show that C/EBPdelta physically interacts with Runx2 and that C/EBPdelta overexpression increases binding between the Runx2-C/EBPdelta complex and the OSE2 element, a critical osteoblast-specific cis-acting element in the OG2 promoter. Consistent with these DNA binding data, a mutation in OSE2 abrogated the stimulatory effect of C/EBPdelta on this promoter activity. Finally, chromatin immunoprecipitation analysis in MC3T3-E1 cells showed in vivo occupancy of the OG2 promoter by Runx2 and C/EBPdelta. In conclusion, C/EBPdelta was found to regulate mouse osteocalcin OG2 promoter activity indirectly by interacting with Runx2 in the context of the OSE2 element and this subsequently resulted in the cooperative activation of the OG2 promoter.
ISSN
0952-5041 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16720721

http://hdl.handle.net/10371/22182
DOI
https://doi.org/10.1677/jme.1.01944
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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