Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression.

Integrative Biology : Quantitative Biosciences From Nano to Macro
Kathryn Miller-JensenDavid V Schaffer

Abstract

Higher order chromatin structure in eukaryotes can lead to differential gene expression in response to the same transcription factor; however, how transcription factor inputs integrate with quantitative features of the chromatin environment to regulate gene expression is not clear. In vitro models of HIV gene regulation, in which repressive mechanisms acting locally at an integration site keep proviruses transcriptionally silent until appropriately stimulated, provide a powerful system to study gene expression regulation in different chromatin environments. Here we quantified HIV expression as a function of activating transcription factor nuclear factor-κB RelA/p65 (RelA) levels and chromatin features at a panel of viral integration sites. Variable RelA overexpression demonstrated that the viral genomic location sets a threshold RelA level necessary to induce gene expression. However, once the induction threshold is reached, gene expression increases similarly for all integration sites. Furthermore, we found that higher induction thresholds are associated with repressive histone marks and a decreased sensitivity to nuclease digestion at the LTR promoter. Increasing chromatin accessibility via inhibition of histone deacetylation...Continue Reading

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Citations

Jul 21, 2015·Cellular and Molecular Bioengineering·Victor C WongKathryn Miller-Jensen
Nov 27, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Prajit LimsirichaiDavid V Schaffer
Aug 22, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jonas DemeulemeesterZeger Debyser
Jul 30, 2014·Biotechnology and Bioengineering·Ashley L FritzDavid V Schaffer
Jul 4, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ramesh RamjiKathryn Miller-Jensen
May 7, 2015·Molecular Systems Biology·Siddharth S DeyAdam P Arkin
May 31, 2018·Aging·Oleg DenisenkoKarol Bomsztyk
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Feb 22, 2013·Current Opinion in HIV and AIDS·Angela Ciuffi, Amalio Telenti
Jan 19, 2018·Cell Reports·Victor C WongKathryn Miller-Jensen

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