The Notch-responsive transcription factor Hes-1 attenuates osteocalcin promoter activity in osteoblastic cells
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-10-12Keywords
Amino Acid MotifsAmino Acid Sequence
Animals
Basic Helix-Loop-Helix Transcription
Factors
Biological Markers
E-Box Elements
Gene Expression Regulation
Homeodomain Proteins
Mice
Molecular Sequence Data
Organ Specificity
Osteoblasts
Osteocalcin
*Promoter Regions, Genetic
Protein Binding
Rats
Receptors, Notch
Repressor Proteins
Transcription, Genetic
Cell Biology
Metadata
Show full item recordAbstract
Notch signaling plays a key role in osteoblast differentiation. A major transcriptional downstream regulator of this pathway is the helix-loop-helix (HLH) transcription factor Hairy/Enhancer of Split 1 (Hes-1). Here we investigated the function of Hes-1 in osteoblastic cells. Endogenous Hes-1 gene expression decreases during progression of bone cell phenotype development in MC3T3-E1 osteoblasts suggesting that it is a negative regulator of osteoblast differentiation. Forced expression of Hes-1 inhibits osteocalcin (OC) mRNA levels, and luciferase assays indicate that Hes-1 directly represses OC promoter activity. In vitro and in vivo protein/DNA interaction assays reveal that recombinant Hes-1 binds specifically to an E-box in the proximal promoter of the OC gene. Deletion of the Hes-1 WRPW domain (MHes-1) that recruits the co-repressor Groucho abrogates repression of OC promoter activity by Hes-1, but also blocks Hes-1 binding to the promoter. The latter result suggests that exogenous Hes-1 may be recruited to the OC promoter by both protein/DNA and protein/protein interactions. We conclude that the Notch-responsive Hes-1 protein is capable of repressing OC gene transcription in osteoblastic cells through an E-box in the proximal promoter. Hes-1 may contribute to osteoblast growth and differentiation by controlling basal bone-specific transcription directly through interactions with transcriptional regulators that are known to bind to the OC gene promoter.Source
J Cell Biochem. 2009 Oct 15;108(3):651-9. Link to article on publisher's siteDOI
10.1002/jcb.22299Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49601PubMed ID
19670267Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/jcb.22299