A chromatin-mediated mechanism for specification of conditional transcription factor targets

Organisms respond to changes in their environment, and many such responses are initiated at the level of gene transcription. Here, we provide evidence for a previously undiscovered mechanism for directing transcriptional regulators to new binding targets in response to an environmental change. We show that Rap1, a master regulator of yeast metabolism, binds to an expanded target set upon nutrient depletion despite decreasing protein levels and no evidence of posttranslational modification. Computational analysis predicted that proteins capable of recruiting the chromatin regulator Tup1 acted to restrict the binding distribution of Rap1 in the presence of nutrients. Deletions of TUP1, genes that encode recruiters of Tup1, or chromatin regulators recruited by Tup1, cause Rap1 to bind specifically and inappropriately to low-nutrient targets. These data, combined with whole-genome measurements of nucleosome occupancy and Tup1 distribution, provide evidence for a mechanism of dynamic target specification that coordinates the genome-wide distribution of intermediate-affinity DNA sequence motifs with chromatin-mediated regulation of accessibility to those sites. Keywords: ChIP-chip ChIP-chip