Bevilacqua M A, Faniello M C, Russo T, Cimino F, Costanzo F
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via S. Pansini 5, I-80131 Napoli, Italy.
Biochem J. 1998 Nov 1;335 ( Pt 3)(Pt 3):521-5. doi: 10.1042/bj3350521.
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.
我们分析了核蛋白P/CAF在特定细胞类型中调控人类重链（H）铁蛋白基因转录的作用。P/CAF是一种组蛋白乙酰转移酶，通过与共激活分子p300/CREB结合蛋白（CBP）相互作用被招募到特定启动子。P/CAF促进的组蛋白乙酰化使核小体结构不稳定，从而有助于转录激活。H铁蛋白基因的转录受转录因子B盒结合因子（Bbf）调控，Bbf通过p300/CBP与RNA聚合酶II相连。对来自各种人类组织和细胞系的RNA种类进行的Northern印迹分析表明，H铁蛋白基因在含有高水平P/CAF转录本的细胞中高水平表达。此外，在组成性表达该蛋白水平较低的细胞中瞬时过表达P/CAF可激活由H启动子与Bbf相互作用区域驱动的转录。还通过评估在癌蛋白E1A存在下的现象来探究p300/CBP在P/CAF可能介导的H启动子调控中的作用。这些实验结果表明，在p300/CBP含量有限的情况下，P/CAF也能激活H启动子。我们认为P/CAF是H铁蛋白基因基础转录装置的一个组成部分，不同细胞类型中P/CAF蛋白的相对含量可解释H铁蛋白基因转录的细胞特异性调控。
