RGD Reference Report - HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression. - Rat Genome Database

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HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression.

Authors: Shimizu, E  Selvamurugan, N  Westendorf, JJ  Olson, EN  Partridge, NC 
Citation: Shimizu E, etal., J Biol Chem. 2010 Mar 26;285(13):9616-26. doi: 10.1074/jbc.M109.094862. Epub 2010 Jan 22.
RGD ID: 9681006
Pubmed: PMID:20097749   (View Abstract at PubMed)
PMCID: PMC2843211   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.094862   (Journal Full-text)

Parathyroid hormone (PTH) is a hormone regulating bone remodeling through its actions on both bone formation and bone resorption. Previously we reported that PTH induces matrix metalloproteinase-13 (MMP-13) transcription in osteoblastic cells. Here, we show that histone deacetylase 4 (HDAC4) interacts with Runx2, binds the MMP-13 promoter, and suppresses MMP-13 gene transcription in the rat osteoblastic cell line, UMR 106-01. PTH induces the rapid cAMP-dependent protein kinase-dependent release of HDAC4 from the MMP-13 promoter and subsequent transcription of MMP-13. Knock-out of HDAC4 either by siRNA in vitro or by gene deletion in vivo leads to an increase in MMP-13 expression, and overexpression of HDAC4 decreases the PTH induction of MMP-13. All of these observations indicate that HDAC4 represses MMP-13 gene transcription in bone. Moreover, PTH stimulates HDAC4 gene expression and enzymatic activity at times corresponding to the reassociation of HDAC4 with the MMP-13 promoter and a decline in its transcription. Thus, HDAC4 is a basal repressor of MMP-13 transcription, and PTH regulates HDAC4 to control MMP-13 promoter activity. These data identify a novel and discrete mechanism of regulating HDAC4 levels and, subsequently, gene expression.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to parathyroid hormone stimulus  IEP 9681006; 9681006; 9681006 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
histone deacetylase binding  IPIHdac4 (Rattus norvegicus)9681006 RGD 
transcription factor binding  IPIRunx2 (Rattus norvegicus)9681006 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac3  (histone deacetylase 3)
Hdac4  (histone deacetylase 4)
Hdac6  (histone deacetylase 6)
Runx2  (RUNX family transcription factor 2)


Additional Information