RGD Reference Report - Parathyroid hormone activation of matrix metalloproteinase-13 transcription requires the histone acetyltransferase activity of p300 and PCAF and p300-dependent acetylation of PCAF.

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Parathyroid hormone activation of matrix metalloproteinase-13 transcription requires the histone acetyltransferase activity of p300 and PCAF and p300-dependent acetylation of PCAF.
Authors:	Lee, M Partridge, NC
Citation:	Lee M and Partridge NC, J Biol Chem. 2010 Dec 3;285(49):38014-22. doi: 10.1074/jbc.M110.142141. Epub 2010 Sep 24.
RGD ID:	9590266
Pubmed:	PMID:20870727 (View Abstract at PubMed)
PMCID:	PMC2992235 (View Article at PubMed Central)
DOI:	DOI:10.1074/jbc.M110.142141 (Journal Full-text)
Parathyroid hormone (PTH) regulates the transcription of many genes involved in bone remodeling in osteoblasts. One of these genes is matrix metalloproteinase-13 (MMP-13), which is involved in bone remodeling and early stages of endochondral bone formation. We have previously shown that Mmp-13 gene expression is highly induced by PTH treatment in osteoblastic UMR 106-01 cells, as well as primary osteoblasts. Here, we show that p300/CBP-associated factor (PCAF), in addition to p300 and Runx2, is required for PTH activation of Mmp-13 transcription. PCAF was increasingly recruited to the MMP-13 proximal promoter region after PTH treatment, and this was associated with an increase in RNA polymerase II recruitment and histone acetylation. In addition, PTH treatment increased the acetylation of PCAF, a process that required p300. Knockdown of PCAF, p300, or Runx2 by siRNA decreased Mmp-13 mRNA expression after PTH treatment in both UMR 106-01 cells and primary osteoblasts. We found that there is a mutual dependence between p300 and PCAF to be recruited to the Mmp-13 promoter after PTH treatment. In promoter-reporter assays, p300 and PCAF had an additive effect on PTH stimulation of MMP-13 promoter activity, and this required their histone acetyltransferase activity. Our findings demonstrate that PCAF acts downstream of PTH signaling as a transcriptional coactivator that is required for PTH stimulation of MMP-13 transcription. PCAF cooperates with p300 and Runx2 to mediate PTH activation of MMP-13 transcription.

Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Kat2b	Rat	cellular response to parathyroid hormone stimulus		IEP			RGD
Kat2b	Rat	positive regulation of chromatin binding		IMP		Ep300	RGD
Kat2b	Rat	positive regulation of transcription by RNA polymerase II		IMP			RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Kat2b	Rat	chromatin		IDA			RGD

Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Kat2b	Rat	chromatin binding		IDA			RGD
Kat2b	Rat	histone acetyltransferase binding		IPI	Ep300 (Rattus norvegicus)		RGD
Ep300	Rat	protein binding		IPI	Kat2b (Rattus norvegicus)		RGD

Genes (Rattus norvegicus)


Ep300 (E1A binding protein p300)	Kat2b (lysine acetyltransferase 2B)

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Parathyroid hormone activation of matrix metalloproteinase-13 transcription requires the histone acetyltransferase activity of p300 and PCAF and p300-dependent acetylation of PCAF.