Histone acetylation and recruitment of serum responsive factor and CREB-binding protein onto SM22 promoter during SM22 gene expression.
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 the coactivator CREB-binding protein (CBP) 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 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 evidence that chromatin acetylation is involved in smooth muscle cell-specific gene regulation.
Qiu
Ping
P
Program in Molecular and Cellular Cardiology, Department of Internal Medicine, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Mich 48201, USA.
Li
Li
L
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D009130:Muscle, Smooth / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020218:Response Elements; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D051879:Twist-Related Protein 1
D002843:Chromatin; D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor; C058992:Tagln protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C497754:Twist1 protein, rat; C051615:transgelin; C012589:trichostatin A; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; C494365:Crebbp protein, rat; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases