Communication between homologous chromosomes: genetic alterations at a nuclease-hypersensitive site can alter mitotic chromatin structure at that site both in cis and in trans.

In vegetatively growing diploid strains of the yeast Saccharomyces cerevisiae, homologous chromosomes appear to be paired via multiple interstitial interactions, likely as a regular feature of the diploid lifestyle. We have previously suggested that this pairing is guided by direct physical interactions between intact DNA duplexes in nuclease-hypersensitive regions and that homology is sensed directly at the DNA level. As a first test of this idea we have examined the level of DNase I sensitivity at a prominent nuclease-hypersensitive site in mitotic chromatin in strains that are either homozygous or heterozygous for a pair of alleles at this site. We find that the degree of nuclease sensitivity at this site on a given (maternal or paternal) chromosome can vary depending upon whether the homologue carries the same allele or the different allele. The data are suggestive that nuclease sensitivity is higher in the former case than in the latter, as though nuclease hypersensitivity might be increased when the two alleles match as compared to when they do not. Formally, these observations suggest that homologous chromosomes can communicate via a mechanism that senses the status of the assayed nuclease-hypersensitive site with resultant changes in chromatin structure at that site. The observed pattern of effects is fully compatible with direct physical interactions between homologues at nuclease-hypersensitive regions, but alternative scenarios also can be envisioned. Since DNase I hypersensitive sites occur in many important regions of chromosomes, homology-dependent interactions involving such regions could potentially affect diverse processes including gene expression (e.g. transvection), chromosome organization, domain structure, and/or DNA replication patterns.