Review
Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes

https://doi.org/10.1016/j.bbaexp.2004.10.005Get rights and content

Abstract

By regulating the structure of chromatin, ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in the maintenance, transmission and expression of the eukaryotic genome. Although all known chromatin-remodeling complexes contain an ATPase as a central motor subunit, a number of distinct classes have been recognized. Recent studies have emphasized a more extensive functional diversification among closely related chromatin remodeling complexes than previously anticipated. Here, we discuss recent insights in the functional differences between two evolutionary conserved subclasses of SWI/SNF-related chromatin remodeling factors. One subfamily comprises yeast SWI/SNF, fly BAP and mammalian BAF, whereas the other subfamily includes yeast RSC, fly PBAP and mammalian PBAF. We review the subunit composition, conserved protein modules and biological functions of each of these subclasses of SWI/SNF remodelers. In particular, we will focus on the roles of specific subunits in developmental gene control and human diseases. Recent findings suggest that functional diversification among SWI/SNF complexes allows the eukaryotic cell to fine-tune and integrate the execution of diverse biological programs involving the expression, maintenance and duplication of its genome.

Section snippets

Introduction: ATP-dependent chromatin remodeling complexes

A single human genome is about 2-m long and must be compacted to fit into a nucleus with a diameter that is about 200,000-fold smaller. Eukaryotic cells have solved this packaging problem by folding their DNA into a highly compacted chromatin structure. However, chromatin needs to be restructured, in order to make the DNA accessible for processes such as gene expression, DNA replication, repair or recombination. One molecular solution to this problem is provided by the activities of a class of

The distinction between two SWI/SNF subclasses is conserved throughout eukaryotic evolution

The ySWI/SNF complex was the first chromatin-remodeling complex to be described. The genes encoding its various subunits were originally identified in two independent screens for mutants affecting either mating type switching or growth on sucrose [14], [15]. Hence, the names Switching defective (SWI) and Sucrose nonfermenting (SNF). Genetic studies revealed that several mutations that suppressed swi/snf phenotypes corresponded to histone genes, providing a direct connection between chromatin

Structural domains and their molecular functions

Below, we review the distinct subunits and their conserved structural domains, which determine the functional properties of the multiprotein assembly of which they are part. Because the subunits of the SWI/SNF remodelers are well conserved, we focus mainly on the Drosophila BAP and PBAP complexes to illustrate their composition and modular structures (Fig. 4). Structural domains were identified using the SMART webtool (http://www.smart.embl-heidelberg.de/smart/show_motifs.pl). The central core

Different SWI/SNF complexes for different occasions

In yeast cells, RSC is much more abundant than ySWI/SNF and plays a more global role in chromatin control. In light of the strict evolutionary conservation of the distinction between two subclasses of SWI/SNF remodelers, it is therefore perhaps paradoxical that in human cells BAF appears to be more abundant than PBAF [20], [90]. The fly contains approximately equal amounts of BAP and PBAP, which bind a comparable number of chromosomal sites on polytene chromosomes [32]. These results indicate

Acknowledgements

We thank Gill Chalkley and Debbie van den Berg for comments on the manuscript and Karin Langenberg for Fig. 7. This work was supported in part by grants from NWO Chemical Sciences and the Dutch Cancer Society, KWF.

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