辅调节因子在核受体基因表达调控中的作用

The Role of Nuclear Receptor Coregulation in Regulation of Gene Expression

核受体 ( nuclear receptor)在增强或抑制基因转录时 ,需借助于诸多辅调节因子的协同作用 ,使调节更为精细、有效及特异 .辅调节因子 ( coregulator)可区分为辅激活因子 ( coactivator)和辅抑制因子 ( corepressor)两大类 ,均具有多种功能各异的蛋白质因子 ,分别汇聚于核受体上构成不同复合体 .它们的主要作用机理是 :( 1 )促使核小体中的组蛋白乙酰基化 ,导致与 DNA的结合松散 ;或脱乙酰基 ,而使组蛋白与 DNA的结合回复紧密状态 ,从而创造一个有利于转录或封闭转录的局部环境 ;( 2 )作用于通用转录因子及 RNA聚合酶 ,以激活转录或抑制转录 .

Nuclear receptors are ligand inducible transcription factors.Nuclear receptor coregulators are coactivators,corepressors or cointegrators that are required by nuclear receptors for efficient transcriptional regulation.However,these proteins do not interact directly with DNA.Liganded receptors will recruit multiple coregulator proteins which may have specific functions during trascriptional initiation.eg.members of the SRC family are group of structurally and functionally related transcriptional coactivators,which can contact and activate basal transcription factors.CBP/P300 is proposed to integrate diverse afferent signals to promoters and have intrinsic histone acetyltransferase activity which is believed to disrupt the nucleosomal structure at these promoters.SMRT and NCoR are corepressors that act to silence gene transcription through interactions with DNA bound proteins.Transcriptional control is a multistep finely regulated process.It is anticipated that further study of nuclear receptor coregulators and their complexes will yield significant insights into the basis of the complexity of regulation of gene transcription.