Maintenance of Heterochromatin Boundary and Nucleosome Composition at Promoters by the Asf1 Histone Chaperone and SWR1-C Chromatin Remodeler in Saccharomyces cerevisiae

摘要

Chromatin remodeling complexes cooperate to regulate gene promoters and to define chromatin neighborhoods. Here, we identified genetic and functional connections between two silencing-related chromatin factors in the maintenance of native heterochromatic structures and nucleosome composition at promoters. Building on a previously reported link between the histone chaperone [Asf1][1] and the [Yaf9][2] subunit of the SWR1-C chromatin remodeler, we found that [ASF1][1] broadly interacted with genes encoding for SWR1-C subunits. [Asf1][1] and [Yaf9][2] were required for maintaining expression of heterochromatin-proximal genes and they worked cooperatively to prevent repression of telomere-proximal genes by limiting the spread of SIR complexes into nearby regions. Genome-wide [Sir2][3] profiling, however, revealed that the cooperative heterochromatin regulation of [Asf1][1] and SWR1-C occurred only on a subset of yeast telomeres. Extensive analyses demonstrated that formation of aberrant heterochromatin structures in the absence of [ASF1][1] and [YAF9][2] was not causal for the pronounced growth and transcriptional defects in cells lacking both these factors. Instead, genetic and molecular analysis revealed that H3K56 acetylation was required for efficient deposition of [H2A.Z][4] at subtelomeric and euchromatic gene promoters, pointing to a role for Asf1-dependent H3K56 acetylation in SWR1-C biology. [1]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000003651 [2]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000005051 [3]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000002200 [4]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000005372