Mechanisms of ATP dependent chromatin remodeling

Abstract

The inter-relationship between DNA repair and ATP dependent chromatin remodeling has begun to become very apparent with recent discoveries. ATP dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. These remodeling complexes are often categorized based on the domain organization of their catalytic subunit. The biochemical properties and structural information of several of these remodeling complexes are reviewed. The different models for how these complexes are able to mobilize nucleosomes and alter nucleosome structure are presented incorporating several recent findings. Finally the role of histone tails and their respective modifications in ATP-dependent remodeling are discussed.

Figure 1

Similarity of different ATP dependent remodeling complexes in S.cerevisiae. Clustering of complexes into different subfamilies is dependent on the sequence homology between the members of the subfamily.

Figure 2

Subunit composition of members of each subfamily of remodeling complexes. The catalytic subunit is marked by an asterisk on the side. Subunits which are shared by multiple complexes in the same organism are underlined. Sub units which are homologous in different organisms by virtue of their sequence are shadowed in grey.

Figure 3

Domain organization of the various subunits of different chromatin remodeling complexes. (A) Shown are the domains that have been found in three of the SWI/SNF subunits, namely Snf2, Snf5, and Swi3. (B) The catalytic subunit of the ISWI complexes from yeast and flies are compared, as well as that of the large accessory subunit of CHRAC/ACF and ISW2. (C) The domain organization of the catalytic subunit of the INO80 complex is shown. The abbreviations for the different domains are bromo for bromo domain, ‘Q’ represents the Q rich region, ‘CC’ for coiled coil region, ‘R/K’ for Arginine/Lysine rich basic region, and ‘LZ’ for Leucine Zipper.

Figure 4

Nucleosome interactions by ISW2. ISW2 interacts at three distinct sites on the nucleosome – linker DNA, 10bp into entry/exit site and two helical turns away from the dyad axis (SHL-2)[130]. Itc1p interacts predominantly with the linker DNA and is represented in red. Isw2p interacts with linker DNA close to the entry/exit site and near SHL2 and is represented in black. Regions where both Isw2p and Itc1p are present are represented in blue. Dpb4p interaction is restricted to the linker DNA and is represented by green circles.

Figure 5

Two models for nucleosome remodeling. (A) SWI/SNF interacts with a large section of nucleosomal DNA and this interaction may facilitate in peeling DNA off the surface of the histone octamer. The generation of a large DNA loop on the surface of the histone octamer would next propagate along the nucleosome surface [129]. (B) Unlike SWI/SNF, ISW2 generates smaller bulges of ∼10bp by a concerted action of two contact points along the nucleosomal DNA – one at SHL2 and the other at the entry/exit site and extranucleosomal DNA (1 and 2) [129]. After formation of the bulge, the bulge is allowed to move in the correct position by release of the contact at SHL2 (3). (C) The RSC model with generation of a 1bp wave by a concerted action between the torsion and tracking domains within the ATPase motif of Sth1p. The 1bp wave propagates along the nucleosomal DNA as depicted [132]