PT  - JOURNAL ARTICLE
AU  - Nikhil Ram-Mohan
AU  - Simone A Thair
AU  - Ulrike M Litzenburger
AU  - Steven Cogill
AU  - Nadya Andini
AU  - Xi Yang
AU  - Howard Y Chang
AU  - Samuel Yang
TI  - Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection
AID  - 10.26508/lsa.202000976
DP  - 2021 Aug 01
TA  - Life Science Alliance
PG  - e202000976
VI  - 4
IP  - 8
4099  - https://www.life-science-alliance.org/content/4/8/e202000976.short
4100  - https://www.life-science-alliance.org/content/4/8/e202000976.full
SO  - Life Sci. Alliance2021 Aug 01; 4
AB  - Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after Escherichia coli exposure for 1 and 4 h along with ATAC-seq. ATAC-seq of neutrophils facilitates detection of pathogen DNA. In addition, despite similarities in genomic distribution of differential chromatin changes across challenges, only a fraction overlaps between the challenges. Ligands depict shared signatures, but majority are unique in position, function, and challenge. Epigenomic changes are plastic, only ∼120 are shared by E. coli challenges over time, resulting in varied differential genes and associated processes. We identify three classes of gene regulation, chromatin access changes in the promoter; changes in the promoter and distal enhancers; and controlling expression through changes solely in distal enhancers. These and transcription factor footprinting reveal timely and challenge specific mechanisms of transcriptional regulation in neutrophils.