SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions

Abstract

Chromatin-remodeling enzymes play essential roles in many biological processes, including gene expression, DNA replication and repair, and cell division. Although one such complex, SWI/SNF, has been extensively studied, new discoveries are still being made. Here, we review SWI/SNF biochemistry; highlight recent genomic and proteomic advances; and address the role of SWI/SNF in human diseases, including cancer and viral infections. These studies have greatly increased our understanding of complex nuclear processes.

FIGURE 1.

Subunits of S. cerevisiae and human SWI/SNF complexes. Each box represents a SWI/SNF subunit that is encoded by a separate gene. In S. cerevisiae, the SWI/SNF family encompasses both its namesake, yeast SWI/SNF, and the closely related but more abundant RSC (remodeling the structure of chromatin) complex, which has different roles from yeast SWI/SNF (–94). In humans, the SWI/SNF family includes both the BAF and PBAF subclasses. The number of amino acids in the longest known isoform is shown in parentheses. Subunits that share homology or that are closely related in function are shown in the same color. The braces grouping multiple subunits indicate that only one of the individual subunits is present in a given complex. Not all subunits are present in all tissues, and additional subunits and complexes that are tissue-specific are likely to be discovered. BAF250A, BAF250B, and BAF200 are also known as ARID1A, ARID1B, and ARID2, respectively.

FIGURE 2.

Histograms showing the frequencies of UniProt keywords for proteins that co-purify with SWI/SNF factors. The keywords shown were retrieved from the UniProt Database for proteins that co-purify with a SWI/SNF factor for HeLa cells (A; data taken from Table S10 in Ref. 45) and mouse ES cells (B; data taken from Table S1 in Ref. 15). Multiple keywords may be associated with a single protein.

FIGURE 3.

Speculative representation of SWI/SNF roles and interactions. The interactions displayed (black chevrons) are derived from multiple data types, particularly as summarized in Refs. (Table S10), (Table S1), and –. SWI/SNF subunits are shown in yellow. For simplicity, an intact nucleus is shown. In addition to the known transcriptional roles of SWI/SNF, it may also participate in chromatin and nuclear organization. All of these functions have potential disease implications. RNA Pol II, RNA polymerase II; TFs, transcription factors.