Early sequencing efforts led to the realization that ATP-dependent chromatin remodeling was a mechanism likely to be used extensively. In mammals, 29 genes are predicted to encode ATPases similar to the yeast SWI2/SNF2 protein. Genetically, these ATPases are nearly all nonredundant, indicating that they play specific biologic roles and their mutations give rise to specific phenotypes and diverse human diseases, as will be discussed below. Biochemical studies in yeast, flies, and mammals have heralded a complete or near-complete characterization of all the subunits of several of the ATP-dependent chromatin remodeling complexes. Perhaps the most well studied of the complexes, the SWI/SNF complex, has evolved extensively in the past 500 million years from yeast to mammals (Fig. 1). The steps in this evolutionary process illustrate well how this fundamental mechanism of chromatin regulation has adapted to accommodate changes in strategies of gene regulation.
