ATP-dependent remodeling and acetylation as regulators of chromatin fluidity

It has become widely accepted that modification of nucleosome structure is an important regulatory mechanism. The hypothesis that the acetylation of histones is involved in regulation was first formed over thirty years ago by Allfrey and colleagues (Allfrey et al. 1964). Subsequent genetic studies suggested that complexes that utilize ATP hydrolysis to alter chromatin structure might also play a regulatory role. In the past 5 years, numerous ATP-dependent remodeling complexes, acetyltransferases, and acetyltransferase complexes have been isolated and characterized. With the identification of these complexes, it is now possible to examine how these complexes modulate gene expression, and how the action of these complexes can be coordinated. The two major classes of chromatin modifying complexes that have been characterized differ in whether or not they use covalent modification to alter chromatin structure (recent reviews include Felsenfeld et al. 1996; Hartzog and Winston 1997; Tsukiyama and Wu 1997; Gregory and Horz 1998; Imhof and Wolffe 1998; Kadonaga 1998; Kuo and Allis 1998; Mizzen and Allis 1998; Pollard and Peterson 1998; Varga-Weisz and Becker 1998; Workman and Kingston 1998). The first class consists of histone acetyltransferase (HAT) and deacetylase complexes, which, respectively, add and remove acetyl groups from the amino termini of the four core histones; increased acetylation is usually (but not always) associated with activation of gene expression, whereas decreased acetylation is associated with repression of gene expression. The second class consists of ATP-dependent chromatin remodeling complexes, which alter chromatin structure by changing the location or conformation of the nucleosome. These structural changes are accomplished without covalent modification, and can be involved in either activation or repression. In addition to these two major classes of complexes, there are also other recently identified complexes such as FACT, DRIP/ARC, and SPT4/SPT5 that help the transcription machinery contend with nucleosome structure (Hartzog et al. 1998; LeRoy et al. 1998; Orphanides et al. 1998; Wada et al. 1998; Naar et al. 1999; Rachez et al. 1999). The mode of action of these other complexes is not yet understood. This review focuses on ATP-dependent remodeling complexes and how these complexes interact with acetylation complexes to regulate gene expression.