Conserved regulatory logic at accessible and inaccessible chromatin during the acute inflammatory response in mammals
Open Access
- 25 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-23
- https://doi.org/10.1038/s41467-020-20765-1
Abstract
The regulatory elements controlling gene expression during acute inflammation are not fully elucidated. Here we report the identification of a set of NF-κB-bound elements and common chromatin landscapes underlying the acute inflammatory response across cell-types and mammalian species. Using primary vascular endothelial cells (human/mouse/bovine) treated with the pro−inflammatory cytokine, Tumor Necrosis Factor-α, we identify extensive (~30%) conserved orthologous binding of NF-κB to accessible, as well as nucleosome-occluded chromatin. Regions with the highest NF-κB occupancy pre-stimulation show dramatic increases in NF-κB binding and chromatin accessibility post-stimulation. These ‘pre-bound’ regions are typically conserved (~56%), contain multiple NF-κB motifs, are utilized by diverse cell types, and overlap rare non-coding mutations and common genetic variation associated with both inflammatory and cardiovascular phenotypes. Genetic ablation of conserved, ‘pre-bound’ NF-κB regions within the super-enhancer associated with the chemokine-encoding CCL2 gene and elsewhere supports the functional relevance of these elements.This publication has 132 references indexed in Scilit:
- Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral TranscriptionCell Reports, 2013
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Comparative Epigenomic Analysis of Murine and Human AdipogenesisCell, 2010
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Identification and Characterization of Enhancers Controlling the Inflammatory Gene Expression Program in MacrophagesImmunity, 2010
- Noncooperative Interactions between Transcription Factors and Clustered DNA Binding Sites Enable Graded Transcriptional Responses to Environmental InputsMolecular Cell, 2010
- ChIP-seq: Using high-throughput sequencing to discover protein–DNA interactionsMethods, 2009
- Prep1/Pbx2 complexes regulate CCL2 expression through the −2578 guanine polymorphismGenes & Immunity, 2008
- Shared Principles in NF-κB SignalingCell, 2008
- A Chromatin Landmark and Transcription Initiation at Most Promoters in Human CellsCell, 2007