Trends in Genetics
Volume 16, Issue 8, 1 August 2000, Pages 345-351
Journal home page for Trends in Genetics

Review
The Swi/Snf family: nucleosome-remodeling complexes and transcriptional control

https://doi.org/10.1016/S0168-9525(00)02060-6Get rights and content

Abstract

The Swi/Snf family of nucleosome-remodeling complexes has been shown to play important roles in gene expression throughout eukaryotes. Genetic and biochemical studies previously suggested that Swi/Snf activates transcription by remodeling nucleosomes, thereby permitting increased access of transcription factors for their binding sites. Recent studies have identified additional Swi/Snf biochemical activities and have suggested possible mechanisms by which Swi/Snf is targeted to specific promoters. Surprisingly, studies have also revealed that, besides being necessary for activation, Swi/Snf is required for transcriptional repression of some genes. These analyses have transformed our understanding of the function of the Swi/Snf family of complexes and suggest that they control transcription in diverse ways.

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.

References (80)

  • J.A. Armstrong

    A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro

    Cell

    (1998)
  • B.R. Cairns

    Two actin-related proteins are shared functional components of the chromatin-remodeling complexes RSC and SWI/SNF

    Mol. Cell

    (1998)
  • K. Zhao

    Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling

    Cell

    (1998)
  • F.C. Holstege

    Dissecting the regulatory circuitry of a eukaryotic genome

    Cell

    (1998)
  • M.P. Cosma

    Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter

    Cell

    (1999)
  • K.E. Neely

    Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays

    Mol. Cell

    (1999)
  • K. Natarajan

    Transcriptional activation by Gcn4p involves independent interactions with SWI/SNF complex and SRB/Mediator

    Mol. Cell

    (1999)
  • D. Dimova

    A role for transcriptional repressors in targeting the yeast Swi/Snf complex

    Mol. Cell

    (1999)
  • E. Kowenz-Leutz et al.

    A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes

    Mol. Cell

    (1999)
  • C.J. Wilson

    RNA polymerase II holoenzyme contains SNF/SWI regulators involved in chromatin remodelling

    Cell

    (1996)
  • B.R. Cairns

    RSC, an essential, abundant chromatin-remodeling complex

    Cell

    (1996)
  • P.S. Knoepfler et al.

    Sin meets NuRD and other tails of repression

    Cell

    (1999)
  • K.E. Brown

    Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin

    Cell

    (1997)
  • J. Kim

    Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes

    Immunity

    (1999)
  • A.P. Bird et al.

    Methylation-induced repression - belts, braces, and chromatin

    Cell

    (1999)
  • P.W. Sternberg

    Activation of the yeast HO gene by release from multiple negative controls

    Cell

    (1987)
  • J.L. Workman et al.

    Alteration of nucleosome structure as a mechanism of transcriptional regulation

    Annu. Rev. Biochem.

    (1998)
  • M. Vignali

    ATP-dependent chromatin-remodeling complexes

    Mol. Cell. Biol.

    (2000)
  • R.E. Kingston et al.

    ATP-dependent remodeling and acetylation as regulators of chromatin fluidity

    Genes Dev.

    (1999)
  • R.E. Kingston

    Repression and activation by multiprotein complexes that alter chromatin structure

    Genes Dev.

    (1996)
  • J. Perez-Martin et al.

    The C-terminal domain of Sin1 interacts with the SWI-SNF complex in yeast

    Mol. Cell. Biol.

    (1998)
  • I.M. Gavin et al.

    Interplay of yeast global transcriptional regulators Ssn6p-Tup1p and Swi-Snf and their effect on chromatin structure

    EMBO J.

    (1997)
  • J.N. Hirschhorn

    Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure

    Genes Dev.

    (1992)
  • E. Matallana

    Chromatin structure of the yeast SUC2 promoter in regulatory mutants

    Mol. Gen. Genet.

    (1992)
  • L. Wu et al.

    Evidence that Snf-Swi controls chromatin structure over both the TATA and UAS regions of the SUC2 promoter in Saccharomyces cerevisiae

    Nucleic Acids Res.

    (1997)
  • O. Papoulas

    The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes

    Development

    (1998)
  • J. Quinn

    DNA-binding properties of the yeast SWI/SNF complex

    Nature

    (1996)
  • D.P. Bazett-Jones

    The SWI/SNF complex creates loop domains in DNA and polynucleosome arrays and can disrupt DNA-histone contacts within these domains

    Mol. Cell. Biol.

    (1999)
  • C. Logie et al.

    Catalytic activity of the yeast SWI/SNF complex on reconstituted nucleosome arrays

    EMBO J.

    (1997)
  • I. Whitehouse

    Nucleosome mobilization catalysed by the yeast SWI/SNF complex

    Nature

    (1999)
  • Cited by (0)

    View full text