title: The replication timing program in the hands of two HDACs.
abstract: 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.
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France. ; Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lengronne
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
keywords: DNA replication; budding yeast; epigenetics; histone deacetylases