NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise

Citations Over TimeTop 10% of 2018 papers

Abstract

Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation. For a given integration site, live-cell imaging shows that NF-κB activation correlates with viral activation, but across integration sites, NF-κB activation cannot account for differences in transcriptional noise and phenotypes. Instead, differences in transcriptional noise are associated with differences in chromatin state and RNA polymerase II regulation. We conclude that, whereas NF-κB regulates transcript abundance in each cell, the chromatin environment modulates noise in the population to support diverse HIV activation in response to TNF.

Related Papers

• → Diversity of core promoter elements comprising human bidirectional promoters(2008)67 cited
• → Heterogeneity of Arabidopsis core promoters revealed by high‐density TSS analysis(2009)112 cited
• → Developing synthetic hybrid promoters to increase constitutive or diauxic shift-induced expression in Saccharomyces cerevisiae(2018)23 cited
• [Review on plant gene promoters].(2004)
• → Constitutive and Regulated Promoters in Yeast: How to Design and Make Use of Promoters inS. cerevisiae(2018)6 cited