Several well-studied promoters in yeast lose nucleosomes upon transcriptional activation and gain them upon repression, an observation that has prompted the model that transcriptional activation and repression requires nucleosome remodeling of regulated promoters. We have examined global nucleosome positioning before and after glucose-induced transcriptional reprogramming, a condition under which more than half of all yeast genes significantly change expression. The majority of induced and repressed genes exhibit no change in promoter nucleosome arrangement, although promoters that do undergo nucleosome remodeling tend to contain a TATA box. Rather, we found multiple examples where the pre-existing accessibility of putative transcription factor binding sites before glucose addition determined whether the corresponding gene would change expression in response to glucose addition. These results suggest that selection of appropriate transcription factor binding sites may be dictated to a large extent by nucleosome prepositioning but that regulation of expression through these sites is dictated not by nucleosome repositioning but by changes in transcription factor activity.
INTRODUCTIONChromatin, whose basic unit is a nucleosome that consists of 147 base pairs of DNA wrapped twice around a histone octamer, plays a central role in the regulation of genes. Several experiments in yeast have shown that nucleosome depletion causes derepression of PHO5, GAL1, CUP1, SUC2, and HIS3 in the absence of their transcriptional activators Durrin et al., 1992;Hirschhorn et al., 1992). These observations suggested that nucleosomes in promoters can function as nonspecific repressors, consistent with the concept that DNA sequences incorporated into nucleosomes are less accessible to DNA binding proteins such as transcription factors (Morse, 2003(Morse, , 2007. Subsequent observations have demonstrated that chromatin structure can participate actively in gene regulation through repositioning of nucleosomes so as to block access of a transcription factor to its cognate binding sites or to remove a barrier to such access. Consistent with this notion, several examples have been reported in which gene induction involves recruitment to a promoter of chromatin remodeling factors and histone modifying activities designed to remove or reposition a nucleosome to allow access to an otherwise masked transcription factor binding site (Li et al., 2007;Williams and Tyler, 2007). For example, remodeling factors act at the above-mentioned promoters for PHO5, GAL1, CUP1, and SUC2 to facilitate nucleosome loss on transcriptional activation and conversely to assemble or stabilize nucleosomes on the gene promoter during transcriptional repression (Almer et al., 1986;Fedor and Kornberg, 1989;Shen et al., 2001;Kim et al., 2006).Chromatin can also play a more passive role in gene regulation by simply controlling which transcription factor binding sites are available for participation in gene regulation. Recent genome-wide studies of nucleosome positioning fo...