Conserved Features of Chromatin Remodeling Enzymes: A Dissertation

Chromatin structure plays an essential role in the regulation' of many nuclear processes such as transcription, replication, recombination, and repair. It is generally accepted that chromatin remodeling is a prerequisite step in gene activation. Over recent years , large multi subunit enzmes that regulate the accessibility of nucleosomal DNA have emerged as key regulators of eukaryotic transcription. It seems likely that similar enzymes contribute to the efficiency of DNA replication, recombination, and repair. These chromatin remodeling complexes can be classified into two broad groups: (1) the A TP-dependent enzymes , which utilize the energy of A TP hydrolysis to increase the accessibility of nucleosomal DNA; and (2) histone modifying enzmes that phosphorylate , acetylate , methylate, ubiquitinate , or ADP-ribosylate the nucleosomal histones (for review see Kingston and Narlikar, 1999; Muchardt and Yaniv, 1999; Brown et ai. , 2000; Vignali et ai. , 2000; Strahl and Allis , 2000). The mechanism by which these two groups of large, multi-subunit enzymes function to alter chromatin structure is enigmatic. Studies suggest that A TP-dependent and histone acety ltransferase chromatin remodeling enzmes have widespread roles in gene expression and perform both independent and overlapping functions. Interestingly, although both groups of enzymes appear to be distinct, several features of these enzmes have been conserved from yeast to man. Thus , understanding the role of these similar features wil be essential in order to elucidate the function of remodeling enzmes, their functional interrelationships , and may uncover the fundamental principals of chromatin remodeling. In this study, we use a combination of yeast molecular genetics and