Molecular cloning and functional characterization of hSNF2

点击翻译按钮获取中文摘要

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.