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  - Integrative profiling of early host chromatin accessibility responses in human neutrophils with sensitive pathogen detection
AID  - 10.1101/2020.04.28.066829
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.28.066829
4099  - http://biorxiv.org/content/early/2020/04/30/2020.04.28.066829.short
4100  - http://biorxiv.org/content/early/2020/04/30/2020.04.28.066829.full
AB  - Sepsis is a leading cause of death globally where neutrophils respond to pathogens via tightly regulated antimicrobial effectors. Combining early neutrophilic responses and pathogen detection may reveal insights for disease recognition. We performed ATAC-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after Escherichia coli (EC) exposure for 1 and 4 hours along with ATAC-seq. ATAC-seq of neurophils retains more pathogenic DNA reads than standard library preparation methods. Only a fraction of differential chromatin regions overlap between challenges. Shared signatures exist for ligands but rest are unique in position, function, and challenge. Epigenomic changes are plastic, only ∼500 are shared by EC challenges over time, resulting in varied differential genes and associated processes. We also identify three classes of chromatin mediated gene regulation based on their relative locations. These and transcription factor footprinting reveal timely and challenge specific mechanisms of transcriptional regulation in neutrophils.Competing Interest StatementH.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, and an advisor to 10x Genomics, Arsenal Biosciences, and Spring Discovery. No other authors have competing interests to report.