Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016504.08608.B9
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Submitted on September 14, 2001
Revised on March 14, 2002
Accepted on March 15, 2002
Histone Acetylation and Recruiting of Serum Responsive Factor and cAMP-Responsive Element--Binding Protein Onto SM22 Promoter During SM22 Gene Expression
Ping Qiu and Li Li *
From the Program in Molecular and Cellular Cardiology, Department of Internal Medicine, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Mich.
* To whom correspondence should be addressed. E-mail: lili{at}med.wayne.edu.
Chromatin acetylation and deacetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) are closely related to eukaryotic gene transcription. Although the binding of serum response factor (SRF) to the CArG boxes in the promoter region is necessary for SM22 expression, it has never been examined whether the local chromatin modification is involved in SM22 gene regulation. In this study, we used the SM22 gene as a model to address whether transcriptional activation of the gene can be manipulated through adjusting histone acetylation of the chromatin template and whether SRF- and HAT-containing coactivators can be recruited onto the SM22 promoter region during gene activation. Here, we showed that the stimulation of the SM22 promoter by coactivators (cAMP-responsive element--binding protein [CBP]/p300 and PCAF) was dependent on HAT activity. Overexpression of HDACs decreased SM22 promoter activity, whereas trichostatin A, an HDAC inhibitor, stimulated SM22 promoter activity in a CArG box--dependent manner and induced endogenous SM22 gene expression. Chromatin immunoprecipitation assays showed that trichostatin A treatment in 10T1/2 cells induces chromatin hyperacetylation in the SM22 gene. Although histone hyperacetylation of the SM22 gene occurred during SM22 gene expression and although SRF and CBP immunocomplexes possess HAT activities in smooth muscle cells, both SRF and CBP were recruited to the CArG box--containing region of the promoter. This study provides initial evidence that chromatin acetylation is involved in SM22 gene regulation.
Key words: SM22 • serum response factor • cAMP-responsive element--binding protein/p300 • histone acetylation • smooth muscle • chromatin immunoprecipitation
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