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

Publication date: Available online 17 November 2016
Source:Cell Host & Microbe
Author(s): Gary Z. Wang, Ying Wang, Stephen P. Goff
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.

Graphical abstract

Teaser

Wang et al. show that histones are rapidly loaded onto newly synthesized retroviral DNAs soon after entry into the nucleus, but before integration into the host genome. Histone marks are added after a delay, and inhibition of histone modifiers enhances transcription from unintegrated viral DNA.


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