A biochemical comparison of the human ATP-dependent nucleosome remodeling proteins SNF2 homolog, SNF2-like, and Brahma-related gene 1

The assembly of the eukaryotic genome into nucleosomes and higher order chromatin structure has a generally repressive effect on gene expression. Genetic and biochemical experiments have led to the identification of a dozen distinct protein complexes, conserved among all eukaryotes studied, which utilize the energy of ATP to counteract the repressive effects of nucleosomes. Several of these complexes are essential for cell survival, and some of these have been linked to the regulation of specific genes. However, the exact mechanisms by which these ATP-dependent nucleosome remodeling complexes work is still not understood.; Nucleosome remodeling complexes can be divided into three classes, based on their protein constituents. These complexes also appear to differ in their genetic roles and their biochemical functions, and complexes from all three classes appear to co-exist in most cells. While each class has been characterized individually, both in vivo and in vitro, there is very little work comparing them directly in vitro. Such a comparison would be very useful in identifying the possible mechanisms by which each class of remodeler functions, and in determining what role each remodeler is most likely to play in vitro.; In my thesis, I have purified the human ATP-dependent nucleosome remodeling proteins SNF2 homolog (SNF2H) and SNF2-like (SNF2L), two members of the ISWI family of remodelers and compared them to the previously-purified BRG1 protein and human SWI/SNF complex, members of the SWI/SNF family of remodelers, in a panel of quantitative biochemical assays. My experiments have revealed functional differences between the two classes of remodelers. I believe that these functional differences are related to mechanistic differences between the different remodelers, and that these mechanistic differences may indicate possible biological differences between the remodeler classes.