title: Nucleosome occupancy as a novel chromatin parameter for replication origin functions.
abstract: Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation.
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Jairo
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.|Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Lee
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Bryony
authors.initials: B
authors.lastname: Lynch
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tsukiyama
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D050505:Mutant Proteins / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics*; D051738:Origin Recognition Complex / Q000235:genetics*; D018741:Replication Origin / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D002843:Chromatin; D050505:Mutant Proteins; D009707:Nucleosomes; C497214:ORC1 protein, S cerevisiae; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins