Functional and Structural Analysis of the Yeast SWI/SNF Complex: a Dissertation

Abstract

Modulating chromatin structure is an important step in maintaining control over the eukaryotic genome. SWI/SNF, one of the complexes belonging to the growing family of ATP-dependent chromatin remodeling enzymes, is involved in controlling the expression of a number of inducible genes whose proper regulation is vital for metabolism and progression through mitosis. The mechanism by which SWI/SNF modulates chromatin structure at the nucleosome level is an important aspect of this regulation. The work in this dissertation focuses on how the Saccharomyces cerevisiae SWI/SNF complex uses the energy of ATP-hydrolysis to alter DNA-histone contacts in nucleosomes. This has been approached in a two part fashion. First, the three-dimensional structure and subunit composition of SWI/SNF complex has been determined. From this study we have identified a potential region of the SWI/SNF complex that might [be] a site for nucleosomal interaction. Second, functional analysis of the ATPase domain of Swi2p, the catalytic subunit of SWI/SNF, has revealed that a specific conserved motif is involved in coupling ATP hydrolysis to the mechanism of chromatin remodeling. These results provide a potential model for the function of the SWI/SNF chromatin remodeling complex at the nucleosome level.