title: Cell cycle regulation of chromatin at an origin of DNA replication.
abstract: Selection and licensing of mammalian DNA replication origins may be regulated by epigenetic changes in chromatin structure. The Epstein-Barr virus (EBV) origin of plasmid replication (OriP) uses the cellular licensing machinery to regulate replication during latent infection of human cells. We found that the minimal replicator sequence of OriP, referred to as the dyad symmetry (DS), is flanked by nucleosomes. These nucleosomes were subject to cell cycle-dependent chromatin remodeling and histone modifications. Restriction enzyme accessibility assay indicated that the DS-bounded nucleosomes were remodeled in late G1. Remarkably, histone H3 acetylation of DS-bounded nucleosomes decreased during late G1, coinciding with nucleosome remodeling and MCM3 loading, and preceding the onset of DNA replication. The ATP-dependent chromatin-remodeling factor SNF2h was also recruited to DS in late G1, and formed a stable complex with HDAC2 at DS. siRNA depletion of SNF2h reduced G1-specific nucleosome remodeling, histone deacetylation, and MCM3 loading at DS. We conclude that an SNF2h-HDAC1/2 complex coordinates G1-specific chromatin remodeling and histone deacetylation with the DNA replication initiation process at OriP.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Charles M
authors.initials: CM
authors.lastname: Chau
authors.forename: Zhong
authors.initials: Z
authors.lastname: Deng
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
authors.forename: Mark-Peter
authors.initials: MP
authors.lastname: Spindler
authors.forename: Aloys
authors.initials: A
authors.lastname: Schepers
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004261:DNA Replication; D044127:Epigenesis, Genetic / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D018741:Replication Origin / Q000235:genetics / Q000502:physiology*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D046911:Macromolecular Substances; D009707:Nucleosomes; D034741:RNA, Small Interfering; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human