ATP-dependent nucleosome remodelling: factors and functions.

The term ‘nucleosome remodelling’ subsumes a large number of ATPdependent changes of canonical nucleosome structure brought about by dedicated nuclear enzymes, which are usually part of larger, multifactorial complexes (Becker and Hörz, 2002; Havas et al., 2001; Lusser and Kadonaga, 2003; Neely and Workman, 2002). Collectively, nucleosome remodelling machines endow chromatin with dynamic properties that implement states of ‘plasticity’ or ‘fluidity’ compatible with the function of chromatin as a substrate for processes revolving around DNA metabolism, such as the expression of genes, the duplication of the genome, the repair of DNA damage and the recombination of chromosomes. Controlled energydependent nucleosome remodelling is vital for faithful execution of a cell’s proliferation and differentiation programme, as perturbations lead to neoplasia and other diseases (Cairns, 2001). Most importantly, ‘remodelling’ of nucleosomes increases the accessibility of DNA sequence elements to regulatory proteins that scan the genome for target sites. In vivo, the action of ATP-dependent nucleosome remodelling machines may lead to a variety of phenomena, ranging from the complete absence of nucleosomes at regulatory sites (Reinke and Horz, 2003) to shifting nucleosome positions (Belikov et al., 2001; Fazzio and Tsukiyama, 2003; Goldmark et al., 2000; Kent et al., 2001; Lomvardas and Thanos, 2001), increasing the access of DNA on the surface of positioned nucleosomes (Truss et al., 1995) and exchange of H2A variants (Krogan et al., 2003; Mizuguchi et al., 2003).