Molecular cloning and functional characterization of hSNF2

酿酒酵母的一系列基因（SWI1, SWI2/SNF2, SWI3， SNF5和SNF6）是多种酵母基因转录所必需的。据报道，哺乳动物糖皮质激素受体在swi1^-， swi2^-或swi3^-菌株中未能激活转录。我们在此报告了两个相互高度相关的人类cdna （hsnf2 α和- β）编码与酵母SWI2/SNF2和果蝇同源的氨基酸序列。它们都含有解旋酶基序、一个溴结构域、高电荷的c端序列和富含脯氨酸、谷氨酰胺和甘氨酸的n端序列。mrna的组织分布有所不同。雌激素受体和视黄酸受体激活的转录被这些cdna的表达不同地增强，尽管对一些不响应核受体的启动子没有观察到增强。我们认为，哺乳动物细胞中存在相当于酵母SWI/SNF复合物的全局转录激活因子或全局共激活因子。SNF/SWI复合体通过重塑染色质结构促进酵母中一组特定基因的有效表达。人类SNF/SWI复合物似乎具有类似的亚基组成和功能。人类SNF/SWI复合物的组成部分hSNF2a/b特异性地与TMF相互作用，TMF先前被鉴定为与tata样序列的DNA结合蛋白。TMF与人细胞核提取物中的SNF/SWI复合物共分离。TMF定位于核和高尔基体。TMF的异位表达导致维甲酸受体依赖性和snf增强基因表达的下调。

A set of genes (SWI1, SWI2/SNF2, SWI3, SNF5 and SNF6) of Saccharomyces cerevisiae are required for transcription of a variety of yeast genes. It was reported that the mammalian glucocorticoid receptor failed to activate transcription in swi1^-, swi2^- or swi3^- strains. We report here that two mutually highly related human cDNAs (hSNF2alpha and -beta) encode amino acid sequences homologous to the yeast SWI2/SNF2 and the Drosophila brahma. Both of these contain the helicase motifs, a bromodomain, highly charged C-terminal sequences and N-terminal sequences rich in proline, glutamine and glycine. Tissue distribution of the mRNAs was somewhat different. Transcription activated by the estrogen receptor and the retinoic acid receptors was differentially enhanced by the expression of these cDNAs, although no enhancement was observed for several promoters which do not respond to nuclear receptors. We suggest that global transcriptional activators, or global coactivators, equivalent to the yeast SWI/SNF complex exist in mammalian cells.The SNF/SWI complex facilitates efficient expression of a specific set of genes in yeast through remodelling chromatin structure. The human SNF/SWI complexes appear to share analogous subunit composition and function. The components of the human SNF/SWI complex, hSNF2a/b, specifically interact with TMF which was previously identified as a DNA binding protein to a TATA-like sequence. TMF is co-fractionated with the SNF/SWI complexes in a human cell nuclear extract. TMF localizes in nucleus and Golgi apparatus. Ectopic expression of TMF leads to down-regulation of retinoic acid receptor-dependent and SNF-enhanced gene expression.