Mechanism(s) of SWI/SNF-induced nucleosome mobilization

Abstract

Impediments to DNA access due to assembly of the eukaryotic genome into chromatin are in part overcome by the activity of ATP-dependent chromatin-remodeling complexes. These complexes employ energy derived from ATP hydrolysis to destabilize histone-DNA interactions and alter nucleosome positions, thereby increasing the accessibility of DNA-binding factors to their targets. However, the mechanism by which theses complexes accomplish this task remains unresolved. We review aspects of nucleosome alteration by the SWI/SNF complex, the archetypal remodeling enzyme. We focus on experiments that provide insights into how SWI/SNF induces nucleosome movement along DNA. Numerous biochemical activities have been characterized for this complex, all likely providing clues as to the molecular mechanism of translocation.

Figure 1

Schematic of subunit organization of SWI/SNF family. All SWI/SNF family members contain an ATPase domain, which is flanked by a HSA domain (light gray) at the N-terminal and a bromodomain (dark gray) at the C-terminal. The ATPase domain is comprised of seven ATPase/Helicase subdomains (I–VI) that are structurally split in two parts: Dexx and HELICc. Between motifs III and VI, there is a characteristic short insertion (light gray).

Figure 2

Model for the mechanism of SWI/SNF induced nucleosome mobilization. The enzyme interacts with the nucleosome DNA from about two turns from the dyad (horizontal line) to well into the linker DNA through the DNA-binding domain (DBD). A translocase domain makes critical interactions with the DNA about two turns from the dyad (star). Only the top turn of DNA in the nucleosome is shown (bold line) with associated linker DNA (dashed line). See text for details.