Trends in Genetics
ReviewThe Swi/Snf family: nucleosome-remodeling complexes and transcriptional control
Section snippets
How was Swi/Snf shown to be involved in nucleosome remodeling?
Swi/Snf was initially linked to chromatin structure by the isolation of suppressors of swi/snf mutations in genes encoding histones and other putative chromatin components7, 8. The connection was strengthened by the finding that Swi/Snf is required in vivo for obtaining a transcriptionally active chromatin structure, as judged by increased nuclease sensitivity at the SUC2 promoter9, 10, 11, 12. In vitro studies demonstrated that Swi/Snf complexes could cause ATP-dependent disruption of
Swi/Snf can remodel, slide and mobilize nucleosomes in vitro
Recent biochemical studies show that Swi/Snf possesses an extensive repertoire of biochemical activities (Fig. 1). Swi/Snf can bind to either nucleosomes or DNA in an ATP-independent fashion6, 16, and electron spectroscopic imaging studies have shown that Swi/Snf binding creates loops in either nucleosomal arrays or naked DNA, bringing distant sites into close proximity17. By contrast, the nucleosome-remodeling activity of Swi/Snf is ATP dependent and has been observed by two types of
Why does Swi/Snf contain so many subunits?
Swi/Snf complexes are large, multi-subunit complexes containing eight or more proteins (Table 1). All Swi/Snf complexes studied contain a core set of components conserved with S. cerevisiae Swi/Snf members, including the conserved DNA-dependent ATPase Snf2/Swi2, Snf5 and Swi3 (Ref. 6). A ‘minimum catalytic core’ complex of three SWI/SNF components, BRG1, INI1 and BAF155/BAF170, can remodel both mononucleosomes and nucleosomal arrays24. In addition, BRG1 alone can substitute for the core
What determines Swi/Snf promoter specificity?
Swi/Snf is estimated to control the transcription of no more than 6% of all genes in S. cerevisiae (25, 40). In addition, genome-wide expression analyses in S. cerevisiae suggest that Swi/Snf control is exerted at the level of individual promoters rather than over chromosomal domains25. This promoter specificity of Swi/Snf has been the focus of several recent studies.
A flood of recent data suggests that DNA-binding regulatory proteins recruit Swi/Snf to specific promoters. For example,
Repression by Swi/Snf – how might it happen?
Recent whole-genome mRNA expression studies suggest that Swi/Snf also represses transcription, as almost half of the genes affected in swi/snf mutants have increased mRNA levels25, 40. This finding was unexpected because most early studies, with one exception59, suggested that Swi/Snf activated transcription by overcoming nucleosomal repression. Repression is probably a general property of the Swi/Snf family, as examples of repression have also been observed with S. cerevisiae RSC and SWI/SNF
Swi/Snf is required for maintenance of activated transcription in vivo
An issue that has been of considerable interest is whether or not Swi/Snf is continuously required at Swi/Snf-dependent genes. Several studies have addressed the continued requirement for Swi/Snf in nucleosome remodeling in vitro and have obtained mixed results6. Recent experiments have addressed the continued need for Swi/Snf-dependent activation in vivo by using either an snf2 (Ref. 69) or an snf5 (Ref. 70) conditional mutant of S. cerevisiae to inactivate Swi/Snf subsequent to
Partially redundant roles for Swi/Snf and other transcription complexes in vivo
Substantial evidence exists that transcriptional control by S. cerevisiae Swi/Snf is partially redundant, with transcriptional control being exerted by other complexes, including SAGA and RSC. The first evidence for this possibility came from double mutant analysis: swi/snf mutations allow viability; however, in combination with mutations in certain RSC genes or the gene for SAGA, swi/snf mutations cause either inviability or extremely poor growth31, 79, 80. More specifically, an overlapping
Future perspectives
The significant advances in our understanding of the Swi/Snf nucleosome remodeling complexes over the past two years have set the stage for even more definitive studies. With the development of whole-genome technologies, all promoters that are directly dependent on Swi/Snf will probably be identified. The emerging studies should enable us to create a model of dynamic Swi/Snf function that ascribes a role for Swi/Snf, both in transcriptional activation and in repression, explores its
Acknowledgements
We thank B. Cairns and T. Wu for helpful comments on the manuscript, and L. Bunt for help with preparation of the manuscript. We apologize to those whose work was not cited owing to space restrictions. Work from our laboratory is supported by grants from the NIH.
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