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Cell Host Microbe. 2016 Dec 14;20(6):798-809. doi: 10.1016/j.chom.2016.10.009. Epub 2016 Nov 17.

Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear Entry.

Author information

1
Integrated Program in Cellular, Molecular, and Biophysical Studies, and Medical Scientist Training Program, Columbia University, New York, NY 10032, USA.
2
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
3
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.

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.

KEYWORDS:

chromatin immunoprecipitation; epigenetics; histone; histone modifications; nucleosome; retrovirus

PMID:
27866901
PMCID:
PMC5159289
DOI:
10.1016/j.chom.2016.10.009
[Indexed for MEDLINE]
Free PMC Article

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