Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression.

The arrangement of nucleosomes in chromatin plays a role in transcriptional regulation by restricting the accessibility of transcription factors and RNA polymerase II to cis-acting elements and promoters. For gene activation, the chromatin structure is altered to an open configuration. The mechanism for this process has been extensively analyzed. However, the mechanism by which repressive chromatin is reconstituted to terminate transcription has not been fully elucidated. Here, we investigated the mechanisms by which chromatin is reconstituted in the fission yeast Schizosaccharomyces pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions. We found that the chromatin structure in the region upstream from fbp1 is closed by a two-step process. When cells are returned to glucose-rich medium following glucose starvation, changes in the nucleosome pattern alter the chromatin configuration at the transcription factor binding site to an inaccessible state, after which the nucleosome density upstream from fbp1 gradually increases via histone loading. Interestingly, this histone loading was observed in the absence of the Tup family corepressors Tup11 and Tup12. Analysis of strains carrying either gene disruptions or mutations affecting nine fission yeast histone chaperone genes demonstrated that the histone chaperone Asf1 induces nucleosome loading during glucose repression. These data establish a previously unappreciated chromatin reconstitution mechanism in fbp1 repression.