Coordination of cell signaling, chromatin remodeling, histone modifications, and regulator recruitment in human matrix metalloproteinase 9 gene transcription.
Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the sequential assembly and dynamic formation of transcription complexes on a human promoter under the influence of mitogen signaling. We find that, coincident with activation of the MMP-9 gene, activators, chromatin remodeling complexes, and coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and coordinated order, which is dependent on activation of MEK-1/extracellular signal-regulated kinase and NF-kappa B signaling pathways. Conversely, corepressor complexes are released from the MMP-9 promoter after transcriptional activation. Histone modifications shift from repressive to permissive modifications concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg-1 is required for MMP-9 gene transcription, which is concomitant with initiation of transcription. Therefore, coordination of cell signaling, chromatin remodeling, histone modifications, and stepwise recruitment of transcription regulators is critical to precisely regulate MMP-9 gene transcription in a temporally and spatially dependent manner. Given the important role of MMP-9 in both normal development and pathological conditions, understanding MMP-9 gene regulation is of great relevance.
Ma
Zhendong
Z
Department of Cell Biology, University of Alabama at Birmingham, 35294-0005, USA.
Shah
Reesha C
RC
Chang
Mi Jung
MJ
Benveniste
Etty N
EN
D001665:Binding Sites; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011033:Podophyllin / Q000031:analogs & derivatives* / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D002843:Chromatin; D006657:Histones; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C003170:mitopodozide; D011033:Podophyllin; D020780:Matrix Metalloproteinase 9; D011034:Podophyllotoxin; D013755:Tetradecanoylphorbol Acetate