DNA sequence- and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes

Abstract

Chromatin-remodeling complexes can translocate nucleosomes along the DNA in an ATP-coupled reaction. This process is an important regulator of all DNA-dependent processes because it determines whether certain DNA sequences are found in regions between nucleosomes with increased accessibility for other factors or wrapped around the histone octamer complex. In a comparison of seven different chromatin-remodeling machines (ACF, ISWI, Snf2H, Chd1, Mi-2, Brg1, and NURF), it is demonstrated that these complexes can read out DNA sequence features to establish specific nucleosome-positioning patterns. For one of the remodelers, ACF, we identified a 40-bp DNA sequence element that directs nucleosome positioning. Furthermore, we show that nucleosome positioning by the remodelers ACF and Chd1 is determined by a reduced affinity to the end product of the translocation reaction. The results suggest that the linkage of differential remodeling activities with the intrinsic binding preferences of nucleosomes can result in establishing distinct chromatin structures that depend on the DNA sequence and define the DNA accessibility for other protein factors.

Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites

“…Because an increase of immobile Snf2L+13 was observed, too, binding to these sites occurs also independently of ATPase activity. This observation suggests a mechanism in which increasing the binding affinity of a given remodeler to its nucleosome substrate promotes nucleosome translocation as proposed previously on the basis of in vitro studies (6).…”

“…These comprise several groups of ATPases classified into the Snf2, ISWI, Mi-2, Chd1, Ino80, ERCC6, ALC1, CHD7, Swr1, RAD54, and Lsh subfamilies (5-7). The associated subunits are responsible for the targeting of the remodeling complexes as well as for the regulation of the remodeling activity (6,8). One of the best conserved ATPase families involved in chromatin remodeling is the ISWI family (9).…”

Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy

“…In order to maintain a controlled distribution of distances, nucleosomes need to be repositioned, most likely by ATP-dependent chromatin-remodeling enzymes such as ACF and CHD1 (65)(66)(67)(68)(69). Catalyzed nucleosome repositioning has been the subject of numerous experimental and theoretical studies (5,(70)(71)(72)(73)(74) but the exact mechanism by which these proteins move the histones along the DNA sequence remains unclear, partially because the mechanisms of remodelers can be heavily convoluted with nucleosome positioning effects that are encoded in the DNA.…”

Regulation of ISWI chromatin remodelling activity

“…Structural conformations of remodeller target DNA could also impact the outcome of the remodelling reaction (Rippe et al 2007;Stockdale et al 2006). For instance, nucleosome remodelling by dACF seems to be dependent on a short DNA element with high intrinsic curvature.…”

“…For instance, nucleosome remodelling by dACF seems to be dependent on a short DNA element with high intrinsic curvature. This specific conformation, indeed, has been shown to influence dACF-dependent nucleosome position after the remodelling occurred, thus affecting a new chromatin state (Rippe et al 2007). Moreover, a recent work suggested a mechanism by which a highly curved 40 bp DNA element, specifically recognized by human Acf-1, thermodynamically affects the preferred local positions adopted by yet remodelled nucleosomes (Partensky and Narlikar 2009).…”