Transcriptional outcomes and kinetic patterning of gene expression in response to NF-κB activation

PLoS Biol. 2018 Sep 10;16(9):e2006347. doi: 10.1371/journal.pbio.2006347. eCollection 2018 Sep.

Abstract

Transcription factor nuclear factor kappa B (NF-κB) regulates cellular responses to environmental cues. Many stimuli induce NF-κB transiently, making time-dependent transcriptional outputs a fundamental feature of NF-κB activation. Here we show that NF-κB target genes have distinct kinetic patterns in activated B lymphoma cells. By combining RELA binding, RNA polymerase II (Pol II) recruitment, and perturbation of NF-κB activation, we demonstrate that kinetic differences amongst early- and late-activated RELA target genes can be understood based on chromatin configuration prior to cell activation and RELA-dependent priming, respectively. We also identified genes that were repressed by RELA activation and others that responded to RELA-activated transcription factors. Cumulatively, our studies define an NF-κB-responsive inducible gene cascade in activated B cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • B-Lymphocytes / metabolism
  • Cell Line
  • Gene Expression Regulation*
  • Humans
  • I-kappa B Kinase / metabolism
  • Kinetics
  • NF-kappa B / metabolism*
  • Protein Binding
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic*
  • Up-Regulation / genetics

Substances

  • NF-kappa B
  • Transcription Factor RelA
  • I-kappa B Kinase

Grants and funding

The Intramural Research Program of the NIH, National Institute on Aging. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.