Conserved regulatory logic at accessible and inaccessible chromatin during the acute inflammatory response in mammals

Azad Alizada, Nadiya Khyzha, Liangxi Wang, Lina Antounians, Xiaoting Chen, Melvin Khor, Minggao Liang, Kumaragurubaran Rathnakumar, Matthew T. Weirauch, Alejandra Medina-Rivera, Jason E. Fish () and Michael D. Wilson ()
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Azad Alizada: Genetics and Genome Biology
Nadiya Khyzha: University of Toronto
Liangxi Wang: Genetics and Genome Biology
Lina Antounians: Genetics and Genome Biology
Xiaoting Chen: Cincinnati Children’s Hospital
Melvin Khor: University of Toronto
Minggao Liang: Genetics and Genome Biology
Kumaragurubaran Rathnakumar: Genetics and Genome Biology
Matthew T. Weirauch: Cincinnati Children’s Hospital
Alejandra Medina-Rivera: Genetics and Genome Biology
Jason E. Fish: University of Toronto
Michael D. Wilson: Genetics and Genome Biology

Nature Communications, 2021, vol. 12, issue 1, 1-23

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20765-1

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DOI: 10.1038/s41467-020-20765-1

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