P/CAF/p300 complex binds the promoter for the heavy subunit of ferritin and contributes to its tissue-specific expression.
We analysed the role of the nuclear protein P/CAF in regulating the transcription of the gene for human heavy (H) ferritin in given cell types. P/CAF is a histone acetylase, recruited to specific promoters via interaction with the co-activator molecule p300/CREB-binding protein (CBP). Histone acetylation promoted by P/CAF destabilizes the nucleosome structure, thus contributing to activation of transcription. The transcription of the H ferritin gene is regulated by the transcription factor B-box-binding factor (Bbf), which bridges RNA polymerase II via p300/CBP. Northern blot analyses of RNA species from various human tissues and cell lines demonstrate that the H ferritin gene is expressed at high levels in cells containing high levels of the P/CAF transcript. Moreover, transient overexpression of P/CAF in cells constitutively expressing low levels of this protein activates transcription driven by the region of the H promoter interacting with Bbf. The involvement of p300/CBP in the possible P/CAF-mediated regulation of H promoter was also explored by evaluating the phenomenon in the presence of the oncoprotein E1A. The results of these experiments demonstrate that P/CAF activates the H promoter also in the presence of limited amounts of p300/CBP. We argue that P/CAF is a component of the basal transcription apparatus of the H ferritin gene and that the relative amounts of the P/CAF protein in different cell types could account for the cell-specific control of the H ferritin gene transcription.
Bevilacqua
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Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via S. Pansini 5, I-80131 Napoli, Italy.
Faniello
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MC
Russo
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Cimino
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Costanzo
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D000123:Acetyltransferases / Q000378:metabolism*; D050882:CREB-Binding Protein; D006528:Carcinoma, Hepatocellular; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005293:Ferritins / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D020014:K562 Cells; D008113:Liver Neoplasms; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D015500:Chloramphenicol O-Acetyltransferase; D005293:Ferritins; D051548:Histone Acetyltransferases; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494363:CREBBP protein, human