Résumé
In eukaryotes, duplication of genomic information depends on the sequential
activation of multiple replication origins distributed along the chromosomes.
Replication origins differ in initiation time, chromatin structure and
three-dimensional position in the nucleus. Recently, we have performed a
systematic analysis of the role of histone deacetylases (HDACs) in the
regulation of origin activity in budding yeast. We have found that the
epigenetic regulation of repetitive sequences is a key determinant of the DNA
replication program. Indeed, our study revealed that two histone deacetylases,
Rpd3 and Sir2, have opposite effects on the replication timing program. Rpd3
delays initiation at late origins, whereas Sir2 promotes efficient activation of
early origins. Remarkably, we also found that Rpd3 and Sir2 regulate initiation
at ~200 replication origins located within the ribosomal DNA (rDNA) array. We
propose that this epigenetic regulation of repetitive origins controls the
replication timing program by modulating the availability of limiting initiation
factors.