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

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 ph

SUBMITTER: Wong VC 

PROVIDER: S-EPMC5812697 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature