Remodelers organize cellular chromatin by counteracting intrinsic histone-DNA sequence preferences in a class-specific manner

We assessed the interplay between DNA sequences and ATP-dependent chromatin remodelers in defining the nucleosomal organization of the eukaryotic genome. We compared the genome-wide distribution and impact on chromatin of NURD, (P)BAP, INO80 and ISWI representing four major families of Drosophila remodelers. Each remodeler has a unique set of genomic targets, and generates distinct chromatin signatures. Remodeler loci have characteristic DNA sequence features, predicted to influence nucleosome formation. Strikingly, remodelers counteract DNA sequence-driven nucleosome distribution in two ways: NURD, (P)BAP and INO80 increase histone density at their target sequences, which disfavor positioned nucleosome formation. In contrast, ISWI promotes open chromatin at sites that are propitious for precise nucleosome placement. Thus, both selective targeting and distinct mechanisms of remodeling underlie the functional differentiation of remodelers. We conclude that chromatin organization involves a class-specific antagonism between remodeler activity and DNA sequence-driven nucleosome placement. The supplementary bed files (P)BAP_sites.bed, NURD_sites.bed, INO80_sites.bed, ISWI_sites.bed contain high quality binding sites for each remodeler obtained by intersecting the sets of significant ChIP-chip peaks for each antibody. Genome-wide remodelers and chromatin profiling in Drosophila by ChIP-chip and FAIRE-chip