Ribosomal DNA silencing by DNA topoisomerase I depends on a Sir2 dependent mechanism
Epigenetic silencing represents a relevant mechanism of transcriptional regulation in S. cerevisiaeand it occurs at the mating-type loci HML, HMR, telomeres and the rDNA repeats. It distinguishes itself from promoter specific gene repression in that the proteins involved in silencing appear to target distal regulatory sites (rather than gene specific promoters) to generate a large domain of repressive chromatin.
Sir2p is a NAD-dependent histone deacetylase, with a preference for removing the acetyl group from K9 and
K14 of histone H3 and K16 of histone H4. The hypoacetylated form of K16 in histone H4 particularly intensifies the binding of Sir3p to histone tails, which further recruits Sir2p and Sir4p. This process repeats itself to permit the spreading of the Sir proteins into the chromosome and further away from telomere ends.
Net1p, another subunit of RENT complex, recruits Sir2p to rDNA and is specifically required for rDNA silencing.
DNA topoisomerase I and DNA topoisomerase II solve topological problems occurring on DNA during its functioning in replication, transcription and recombination. However at ribosomal genes a series of similar phenotypes have been reported to be shared between sir2 and top1 mutants, although the absence of functional and structural similarity between the two enzymes. We wanted to find the connections among these phenotypes.