Cell cycle regulation of chromatin at an origin of DNA replication

Jing Zhou, Charles M. Chau, Zhong Deng, Ramin Shiekhattar, Mark Peter Spindler, Aloys Schepers, Paul M. Lieberman

Research output: Contribution to journalArticle

100 Scopus citations

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 Gl. 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.

Original languageEnglish (US)
Pages (from-to)1406-1417
Number of pages12
JournalEMBO Journal
Volume24
Issue number7
DOIs
StatePublished - Apr 6 2005

Keywords

  • DNA replication
  • EBV
  • Histone
  • OriP
  • SNF2h

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Zhou, J., Chau, C. M., Deng, Z., Shiekhattar, R., Spindler, M. P., Schepers, A., & Lieberman, P. M. (2005). Cell cycle regulation of chromatin at an origin of DNA replication. EMBO Journal, 24(7), 1406-1417. https://doi.org/10.1038/sj.emboj.7600609