title: Linker histone phosphorylation regulates global timing of replication origin firing.
abstract: Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing.
authors.affiliation: 1UMR-CNRS 6204 U3B, Université de Nantes, Dynamique de la Chromatine et Épigénétique, 44322 Nantes, France. Electronic address: christophe.thiriet@univ-nantes.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Thiriet
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642. Electronic address: Jeffrey_Hayes@urmc.rochester.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hayes
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism*; D047468:Immunoprecipitation; D010766:Phosphorylation; D016839:Physarum polycephalum / Q000235:genetics; D018741:Replication Origin
chemical_list: D006657:Histones