title: Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear Entry.
abstract: Chromosomal structure of nuclear DNA is usually maintained by insertion of nucleosomes into preexisting chromatin, both on newly synthesized DNA at replication forks and at sites of DNA damage. But during retrovirus infection, a histone-free DNA copy of the viral genome is synthesized that must be loaded with nucleosomes de novo. Here, we show that core histones are rapidly loaded onto unintegrated Moloney murine leukemia virus DNAs. Loading of nucleosomes requires nuclear entry, but does not require viral DNA integration. The histones associated with unintegrated DNAs become marked by covalent modifications, with a delay relative to the time of core histone loading. Expression from unintegrated DNA can be enhanced by modulation of the histone-modifying machinery. The data show that histone loading onto unintegrated DNAs occurs very rapidly after nuclear entry and does not require prior establishment of an integrated provirus.
authors.affiliation: Integrated Program in Cellular, Molecular, and Biophysical Studies, and Medical Scientist Training Program, Columbia University, New York, NY 10032, USA.
authors.forename: Gary Z
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Biochemistry and Molecular Biophysics and Microbiology and Immunology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA. Electronic address: spg1@cumc.columbia.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002843:Chromatin; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D057890:Epigenomics; D057809:HEK293 Cells / Q000821:virology; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D041681:NIH 3T3 Cells / Q000821:virology; D009707:Nucleosomes / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D012192:Retroviridae Infections / Q000821:virology; D016662:Virus Integration; D053586:Virus Internalization
chemical_list: D002843:Chromatin; D004279:DNA, Viral; D006657:Histones; D009707:Nucleosomes
keywords: chromatin immunoprecipitation; epigenetics; histone; histone modifications; nucleosome; retrovirus