The SWI/SNF chromatin-remodeling complexes utilize energy from ATP hydrolysis to reposition nucleosomes and regulate the expression of human genes. Here, we studied the roles of human Brahma （hBrm） and Brahma-relate...The SWI/SNF chromatin-remodeling complexes utilize energy from ATP hydrolysis to reposition nucleosomes and regulate the expression of human genes. Here, we studied the roles of human Brahma （hBrm） and Brahma-related gene 1 （Brgl）, the ATPase subunits of the SWI/SNF complexes, in regulating human genes. Our results indicate that both hBrm and Brgl interact with Signal transducer and activator of transcription （Stat） 1 in vitro. However, Statl in its native form only recruits hBrm to IFNy-activated sequences （GAS） of individual genes; by contrast, in a stress- induced phosphorylated form, Statl mainly binds to Brgl. Under basal conditions, hBrm is recruited by native Statl to the GAS and exists in a mSin3/HDAC co-repressor complex on the hsp90a gene, which shows a compact chromatin structure. Upon heat-shock, hBrm is acetylated by p300 and dissociates from the co-repressor complex, which the phosphorylated St^tl is increased, and binds and recruits Brgl to the GAS, leading to elevated induction of the gene. This hBrm/Brgl switch also occurs at the GAS of all of the three examined immune genes in heat-shocked cells; how- ever, this switch only occurs in specific cell types upon exposure to IFNy. Regardless of the stimulus, the hBrm/Brgl switch at the GAS elicits an increase in gene activity. Our data are consistent with the hypothesis that the hBrm/Brgl switch is an indicator of the responsiveness of a gene to heat-shock or IFNy stimulation and may represent an ＂on-off switch＂ of gene expression in vivo.展开更多
基金Acknowledgments We thank Drs XY Fu, CM Horvath, AN Imbalzano, HB Zhang, S Cadelwood and K Shuai for kindly providing plasmids, antibodies and chemicals used in this work. We thank Dr Robert A Casero, Jr of the Johns Hopkins University School of Medicine for his critical reading of the manuscript, and Dr Weimin Zhong of the Yale University for his contribution to the work. This work was supported by the National Natural Science Foundation of China （90408007, 30871382 and 30721063）, the National Basic Research Program of China （973 Program） （2005CB522405）, the National Key Scientific Program （2011CB964902） and Special Funds of State Key Laboratories （2060204）.
文摘The SWI/SNF chromatin-remodeling complexes utilize energy from ATP hydrolysis to reposition nucleosomes and regulate the expression of human genes. Here, we studied the roles of human Brahma （hBrm） and Brahma-related gene 1 （Brgl）, the ATPase subunits of the SWI/SNF complexes, in regulating human genes. Our results indicate that both hBrm and Brgl interact with Signal transducer and activator of transcription （Stat） 1 in vitro. However, Statl in its native form only recruits hBrm to IFNy-activated sequences （GAS） of individual genes; by contrast, in a stress- induced phosphorylated form, Statl mainly binds to Brgl. Under basal conditions, hBrm is recruited by native Statl to the GAS and exists in a mSin3/HDAC co-repressor complex on the hsp90a gene, which shows a compact chromatin structure. Upon heat-shock, hBrm is acetylated by p300 and dissociates from the co-repressor complex, which the phosphorylated St^tl is increased, and binds and recruits Brgl to the GAS, leading to elevated induction of the gene. This hBrm/Brgl switch also occurs at the GAS of all of the three examined immune genes in heat-shocked cells; how- ever, this switch only occurs in specific cell types upon exposure to IFNy. Regardless of the stimulus, the hBrm/Brgl switch at the GAS elicits an increase in gene activity. Our data are consistent with the hypothesis that the hBrm/Brgl switch is an indicator of the responsiveness of a gene to heat-shock or IFNy stimulation and may represent an ＂on-off switch＂ of gene expression in vivo.
