Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology
*Base Composition; Chromosomes, Fungal; Gene Expression Regulation, Fungal; Histone Code; Histone Deacetylases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
Genetics and Genomics | Life Sciences | Medicine and Health Sciences
BACKGROUND: Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood.
RESULTS: We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.
CONCLUSION: We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.