학술논문

NF-κB dynamics determine the stimulus specificity of epigenomic reprogramming in macrophages
Document Type
article
Source
Science. 372(6548)
Subject
Genetics
Human Genome
Animals
Cell Nucleus
Chromatin
DNA
Enhancer Elements
Genetic
Epigenome
Gene Expression Regulation
Histones
MAP Kinase Signaling System
Macrophages
Methylation
Mice
Mice
Inbred C57BL
Mice
Knockout
Models
Biological
NF-KappaB Inhibitor alpha
NF-kappa B
Nucleosomes
Signal Transduction
Transcription Factor RelA
Transcription
Genetic
General Science & Technology
Language
Abstract
The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor κB (NF-κB) is a transcription factor that is activated by all pathogen-associated stimuli and can reprogram the epigenome by activating latent enhancers. However, we show that NF-κB does so only in response to a subset of stimuli. This stimulus specificity depends on the temporal dynamics of NF-κB activity, in particular whether it is oscillatory or non-oscillatory. Non-oscillatory NF-κB opens chromatin by sustained disruption of nucleosomal histone-DNA interactions, enabling activation of latent enhancers that modulate expression of immune response genes. Thus, temporal dynamics can determine a transcription factor's capacity to reprogram the epigenome in a stimulus-specific manner.