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Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection
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 fo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321655/ https://www.ncbi.nlm.nih.gov/pubmed/34145026 http://dx.doi.org/10.26508/lsa.202000976 |
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author | Ram-Mohan, Nikhil Thair, Simone A Litzenburger, Ulrike M Cogill, Steven Andini, Nadya Yang, Xi Chang, Howard Y Yang, Samuel |
author_facet | Ram-Mohan, Nikhil Thair, Simone A Litzenburger, Ulrike M Cogill, Steven Andini, Nadya Yang, Xi Chang, Howard Y Yang, Samuel |
author_sort | Ram-Mohan, Nikhil |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8321655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-83216552021-08-04 Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection Ram-Mohan, Nikhil Thair, Simone A Litzenburger, Ulrike M Cogill, Steven Andini, Nadya Yang, Xi Chang, Howard Y Yang, Samuel Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2021-06-18 /pmc/articles/PMC8321655/ /pubmed/34145026 http://dx.doi.org/10.26508/lsa.202000976 Text en © 2021 Ram-Mohan et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Ram-Mohan, Nikhil Thair, Simone A Litzenburger, Ulrike M Cogill, Steven Andini, Nadya Yang, Xi Chang, Howard Y Yang, Samuel Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title | Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title_full | Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title_fullStr | Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title_full_unstemmed | Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title_short | Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
title_sort | profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321655/ https://www.ncbi.nlm.nih.gov/pubmed/34145026 http://dx.doi.org/10.26508/lsa.202000976 |
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