CONICET | Buscador de Institutos y Recursos Humanos

Cellular DNA is packaged into chromatin, which is composed of regularly-spacednucleosomes with occasional gaps corresponding to active regulatory elements, such as promotersand enhancers, called nucleosome-depleted regions (NDRs). This chromatin organisation is primarilydetermined by the activities of a set ofATP-dependent remodeling enzymes that are capable of movingnucleosomes along DNA, or of evicting nucleosomes altogether. In yeast, the nucleosome-spacingenzymes are ISW1 (Imitation SWitch protein 1), Chromodomain-Helicase-DNA-binding (CHD)1,ISW2 (Imitation SWitch protein 2) and INOsitol-requiring 80 (INO80); the nucleosome evictionenzymes are the SWItching/Sucrose Non-Fermenting (SWI/SNF) family, the Remodeling the Structureof Chromatin (RSC) complexes and INO80. We discuss the contributions of each set of enzymesto chromatin organisation. ISW1 and CHD1 are the major spacing enzymes; loss of both enzymesresults in major chromatin disruption, partly due to the appearance of close-packed di-nucleosomes.ISW1 and CHD1 compete to set nucleosome spacing on most genes. ISW1 is dominant, setting wildtype spacing, whereas CHD1 sets short spacing and may dominate on highly-transcribed genes.We propose that the competing remodelers regulate spacing, which in turn controls the binding oflinker histone (H1) and therefore the degree of chromatin folding. Thus, genes with long spacing bindmore H1, resulting in increased chromatin compaction. RSC, SWI/SNF and INO80 are involved inNDR formation, either directly by nucleosome eviction or repositioning, or indirectly by aecting thesize of the complex that resides in the NDR. The nature of this complex is controversial: some suggestthat it is a RSC-bound ?fragile nucleosome?, whereas we propose that it is a non-histone transcriptioncomplex. In either case, this complex appears to serve as a barrier to nucleosome formation, resulting inthe formation of phased nucleosomal arrays on both sides.