SWI/SNF stimulates the formation of disparate activator-nucleosome complexes but is partially redundant with cooperative binding

Abstract

To investigate the potential mechanisms by which the SWI/SNF complex differentially regulates different genes we have tested whether transcription factors with diverse DNA binding domains were able to exploit nucleosome disruption by SWI/SNF. In addition to GAL4-VP16, the SWI/SNF complex stimulated nucleosome binding by the Zn2+ fingers of Sp1, the basic helix- loop-helix domain of USF, and the rel domain of NF-κB. In each case SWI/SNF action resulted in the formation of a stable factor-nucleosome complex that persisted after detachment of SWI/SNF from the nucleosome. Thus, stimulation of factor binding by SWI/SNF appears to be universal. The degree of SWI/SNF stimulation of nucleosome binding by a factor appears to be inversely related to the extent that binding is inhibited by the histone octamer. Cooperative binding of 5 GAL4-VP16 dimers to a 5-site nucleosome enhanced GAL4 binding relative to a single-site nucleosome, but this also reduced the degree of stimulation by SWI/SNF. The SWI/SNF complex increased the affinity of 5 GAL4- VP16 dimers for nucleosomes equal to that of DNA but no further. Similarly, multimerized NF-κB sites enhanced nucleosome binding by NF-κB and reduced the stimulatory effect of SWI/SNF. Thus, cooperative binding of factors to nucleosomes is partially redundant with the function of the SWI/SNF complex.