GLUCOCORTICOID RECEPTOR-DEPENDENT DISRUPTION OF A SPECIFIC NUCLEOSOME ON THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER IS PREVENTED BY SODIUM-BUTYRATE
GLUCOCORTICOID RECEPTOR-DEPENDENT DISRUPTION OF A SPECIFIC NUCLEOSOME ON THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER IS PREVENTED BY SODIUM-BUTYRATE
复制标题
DOI：
10.1073/pnas.87.10.3977
复制
发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
HAGER, GL
中科院分区：
文献类型：
--
作者：
BRESNICK, EH;JOHN, S;HAGER, GL
我们的实验室先前开发了来自小鼠NIH 3T3成纤维细胞和C127乳腺肿瘤细胞的细胞系，这些细胞系在基于牛乳头瘤病毒的附加体中稳定表达小鼠乳腺肿瘤病毒（MMTV）长末端重复融合基因。糖皮质激素强烈地激活从附加体的转录，并诱导MMTV启动子上的定相核小体阵列中的单个核小体的破坏。丁酸钠抑制糖皮质激素依赖性的发展的核酸酶高血压网站，这是由于该核小体的位移，并抑制诱导RNA转录从附加体。饱和结合研究表明，丁酸处理不显着影响糖皮质激素受体的量或糖皮质激素结合亲和力。在瞬时转染试验中，糖皮质激素可以激活转录从MMTV长末端重复驱动的荧光素酶基因构建体在未经处理的和丁酸盐处理的细胞中等效，这表明，所需的MMTV启动子的反式激活的可溶性因子不受丁酸盐的影响。丁酸盐对稳定染色质模板和瞬时表达质粒的诱导的差异效应表明丁酸盐通过诱导染色质的修饰来防止核小体移位并抑制转录。
Our laboratory has previously developed cell lines derived from mouse NIH 3T3 fibroblasts and C127 mammary tumor cells that stably express mouse mammary tumor virus (MMTV) long terminal repeat fusion genes in bovine papillomavirus-based episomes. Glucocorticoid hormone strongly activates transcription from episomes and induces the disruption of a single nucleosome in an array of phased nucleosomes on the MMTV promoter. Sodium butyrate inhibits the glucocorticoid hormone-dependent development of a nuclease-hypertensive site that is due to the displacement of this nucleosome, and inhibits induction of RNA transcripts from episomes. Saturation binding studies show that butyrate treatment does not significantly affect the amount or the hormone-binding affinity of the glucocorticoid receptor. In a transient transfection assay, glucocorticoid hormone can activate transcription from a MMTV long terminal repeat-driven luciferase gene construct equivalently in untreated and butyrate-treated cells, indicating that the soluble factors necessary for transactivation of the MMTV promoter are unaffected by butyrate. The differential effect of butyrate on the induction of stable chromatin templates and transiently expressed plasmids suggests that butyrate prevents nucleosome displacement and repress transcription by inducing a modification of chromatin.