ATP-dependent chromatin-remodeling complexes are conserved among most eukaryotes and function by altering nucleosome structure to permit cellular regulatory elements usage of the DNA. expressed genes revealed no or minimal effects on transcript levels. We propose that the requirement for mammalian SWI-SNF complexes in gene activation events will be specific to individual genes and signaling pathways. The packaging of eukaryotic DNA into nucleosomes and higher order chromatin structure presents cells with a significant barrier to DNA utilization and necessitates mechanisms by which chromatin structure can be modified so that transcription can occur. Many multiprotein complexes with the ability to modify chromatin structure have been identified. These include histone acetyltransferases and deacetylases, which directly modify histone tail domains, and a class of energy-dependent enzymes that utilize ATP hydrolysis to alter nucleosome structure (reviewed in references 23, 30, 32, 34, 70, 83, and 84). The ATP-dependent chromatin remodeling complexes are conserved among eukaryotes, they share a related subunit that possesses DNA-stimulated ATPase activity, and each has been demonstrated to alter nucleosome structure in vitro in an ATP-dependent manner. Most of these complexes can be classified into two groups, those containing homologues of the yeast SWI2-SNF2 ATPase subunit, including yeast SWI-SNF (7, 12, 55), human SWI-SNF (hSWI-SNF) (24, 35, 82), yeast RSC (8), and BRM complexes (54, 71), and those containing homologues of the imitation-switch (ISWI) ATPase gene (16), including yeast ISW1 and ISW2 (76), human RSF (39), and the NURF, CHRAC, and ACF complexes (25, 75, 78). A third group can be defined by and human complexes containing the Mi2 protein, a related ATPase found in association with histone deacetylase activity (72, 81, 87, 90). Although members of the ATP-dependent class of chromatin remodelers facilitate alterations in nucleosome structure in vitro, the cellular role of most of the complexes is not well defined. The yeast SWI-SNF complex is the prototype for the ATP-dependent remodeling complexes. Five of the subunits are encoded by the SWI and SNF genes that were originally isolated in displays for genes necessary for mating type switching or for sucrose fermentation (3, 53, 68). Following work established these genes had been required for the perfect expression of the subset of CD334 inducible candida genes (31, 41, 56, 88) as well as for transcription of Ty components (11, 21, 41). The brm proteins, the ATPase subunit from the brm complicated, has been proven to be always a 414864-00-9 regulator of homeotic genes (71), underscoring a job for this complicated in developmentally regulated gene expression. Human SWI-SNF complexes contain either the human BRM (hBRM) (hSNF2) or the BRG1 (hSNF2) homologues of the yeast SWI2-SNF2 ATPase (10, 29, 51). Components of hSWI-SNF complexes have been implicated in a range of cellular events, including gene activation, regulation of cell growth, and development and differentiation (reviewed in reference 23). Regulation of cell cycle progression may occur via interaction of BRG1-hBRM with the retinoblastoma oncoprotein (Rb) and/or cyclin 414864-00-9 E (14, 62, 65, 69). In addition, the complex or individual subunits may be targeted by viral regulatory proteins upon infection of cells by adenovirus, Epstein-Barr virus, human papillomavirus, and human immunodeficiency virus (13, 28, 37, 43, 86). The ini1 subunit has been shown to interact with the ALL-1 protein, the translocation 414864-00-9 of which is a hallmark of several types of human acute leukemias (58), and ini1 also was found to be altered in human malignant rhabdoid tumors (79), suggesting a role for ini1 as a tumor suppressor. Thus, the human SWI-SNF complex not only has a subunit that may act as a tumor suppressor (ini1) but also contains other subunits that directly interact with Rb,.