Interrelationships between nuclear structure and ligand-activated intracellular receptors.
Interrelationships between nuclear structure and ligand-activated intracellular receptors.
复制标题
DOI：
10.1615/critreveukargeneexpr.v6.i2-3.80
复制
发表时间：
1996
影响因子：
1.6
通讯作者：
M. Ruh;R. Dunn;T. Ruh
中科院分区：
文献类型：
--
作者：
M. Ruh;R. Dunn;T. Ruh
配体激活的细胞内受体在基因表达激活中的作用很可能涉及一个需要改变染色质结构的多步骤过程。类固醇激素受体超家族成员以及转录激活因子的基本区/螺旋-环-螺旋家族的配体激活成员的研究结果表明，两种不同的核结构及其相关的核蛋白在基因激活的初始阶段是重要的：核基质和核小体。细胞和组织特异性的核基质蛋白和组蛋白的变体和修饰似乎是重要的组织和物种特异性的配体诱导的反应。由于受体的功能可能在体内受到启动子和转录因子可及性的限制，因此核配体-受体复合物的各种作用可能涉及与核基质蛋白和/或核小体的相互作用。组织特异性结构核蛋白可以控制DNA的构象（通过基质附着区成环）和核小体的解旋或重排，从而为某些基因的表达提供特异性。基因激活所需的协同元件的调节可能涉及基因启动子与核基质的缔合以及核小体的存在。因此，基因配体-受体激活所涉及的一系列事件需要染色质结构的改变，这使得受体复合物能够接触基因内的元件。
The role of ligand-activated intracellular receptors in activation of gene expression most probably involves a multistep process that requires alteration in chromatin structure. Results of studies with members of the steroid hormone receptor superfamily as well as the ligand-activated member of the basic region/helix-loop-helix family of transcriptional activators suggests that two different nuclear structures and their associated nuclear proteins are important in the initial stages of gene activation: the nuclear matrix and nucleosomes. Cell- and tissue-specific nuclear matrix proteins and the variant and modified histones appear to be important for tissue and species specificity of ligand-induced responses. Because the function of a receptor may be limited in vivo by promoter and transcription factor accessibility, the various roles of nuclear ligand-receptor complexes may involve interaction with nuclear matrix proteins and/or nucleosomes. Tissue-specific structural nuclear proteins could control the conformation (looping through matrix attachment regions) of the DNA and unwinding or rearrangement of nucleosomes, thus providing specificity to the expression of certain genes. Modulation of cooperative elements required for gene activation may involve association of the gene promoter with the nuclear matrix together with the presence of nucleosomes. Thus, the series of events involved in ligand-receptor activation of genes requires alterations in chromatin structure, which allow access of the receptor complex to elements within the gene.