Glucocorticoid receptors recognize DNA sequences in and around murine mammary tumour virus DNA.
Glucocorticoid receptors recognize DNA sequences in and around murine mammary tumour virus DNA.
复制标题
糖皮质激素受体识别小鼠乳腺肿瘤病毒 DNA 内部和周围的 DNA 序列。
作者：
S. Geisse;C. Scheidereit;H. Westphal;N. Hynes;B. Groner;M. Beato
在几种啮齿动物细胞系中，糖皮质激素在糖皮质激素受体介导的过程中增加小鼠乳腺肿瘤病毒（MMTV）前病毒DNA的转录。为了研究受体和诱导基因上的特定序列之间的直接相互作用是否可以参与转录的激素调节，用部分纯化的大鼠肝脏糖皮质激素受体和8个克隆的MMTV前病毒探针进行了过滤结合研究。40 000和90 00 mol.重量受体的形式优先结合含有MMTV长末端重复单元（LTR）的右侧400 - 500个核苷酸的限制性片段。使用LTR缺失突变体，我们确认LTR的右端含有至少一个糖皮质激素受体的结合位点。此外，受体优先结合至少三个内源性前病毒拷贝侧翼的小鼠基因组序列，以及一些内源性和外源性前病毒中env基因内的序列。这些发现与类固醇激素通过激素受体复合物与诱导基因内和周围的DNA序列直接相互作用来调节特定基因表达的假设是一致的。
In several rodent cell lines, glucocorticoids increase the transcription of murine mammary tumour virus (MMTV) proviral DNA in a process mediated by the glucocorticoid receptor. To investigate whether a direct interaction between the receptor and specific sequences on the induced genes can be implicated in the hormonal regulation of transcription, filter binding studies were performed with partially purified glucocorticoid receptor of rat liver and eight cloned MMTV proviral probes. Both the 40 000 and the 90 00 mol. wt. forms of the receptor do bind preferentially to restriction fragments containing the right 400‐500 nucleotides of the MMTV long terminal repeat units (LTR). Using LTR deletion mutants, we confirm that the right end of the LTR contains at least one binding site for the glucocorticoid receptor. In addition, the receptor binds preferentially to the mouse genomic sequences flanking at least three endogenous proviral copies, and to sequences within the env genes in some of the endogenous and exogenous proviruses. These findings are compatible with the hypothesis that steroid hormones regulate specific gene expression through a direct interaction of the hormone‐receptor complex with DNA sequences in and around the induced genes.