Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection
Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and mon...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9439955/ https://www.ncbi.nlm.nih.gov/pubmed/35102304 http://dx.doi.org/10.1038/s41564-021-01049-w |
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author | del Rosario, Ricardo C. H. Poschmann, Jeremie Lim, Carey Cheng, Catherine Y. Kumar, Pavanish Riou, Catherine Ong, Seow Theng Gerges, Sherif Hajan, Hajira Shreen Kumar, Dilip Marzuki, Mardiana Lu, Xiaohua Lee, Andrea Wijaya, Giovani Claresta Rayan, Nirmala Arul Zhuang, Zhong Du Bruyn, Elsa Chee, Cynthia Bin Eng Lee, Bernett Lum, Josephine Zolezzi, Francesca Poidinger, Michael Rotzschke, Olaf Khor, Chiea Chuen Wilkinson, Robert J. Wang, Yee T. Chandy, George K De Libero, Gennaro Singhal, Amit Prabhakar, Shyam |
author_facet | del Rosario, Ricardo C. H. Poschmann, Jeremie Lim, Carey Cheng, Catherine Y. Kumar, Pavanish Riou, Catherine Ong, Seow Theng Gerges, Sherif Hajan, Hajira Shreen Kumar, Dilip Marzuki, Mardiana Lu, Xiaohua Lee, Andrea Wijaya, Giovani Claresta Rayan, Nirmala Arul Zhuang, Zhong Du Bruyn, Elsa Chee, Cynthia Bin Eng Lee, Bernett Lum, Josephine Zolezzi, Francesca Poidinger, Michael Rotzschke, Olaf Khor, Chiea Chuen Wilkinson, Robert J. Wang, Yee T. Chandy, George K De Libero, Gennaro Singhal, Amit Prabhakar, Shyam |
author_sort | del Rosario, Ricardo C. H. |
collection | PubMed |
description | Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens. |
format | Online Article Text |
id | pubmed-9439955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94399552022-09-04 Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection del Rosario, Ricardo C. H. Poschmann, Jeremie Lim, Carey Cheng, Catherine Y. Kumar, Pavanish Riou, Catherine Ong, Seow Theng Gerges, Sherif Hajan, Hajira Shreen Kumar, Dilip Marzuki, Mardiana Lu, Xiaohua Lee, Andrea Wijaya, Giovani Claresta Rayan, Nirmala Arul Zhuang, Zhong Du Bruyn, Elsa Chee, Cynthia Bin Eng Lee, Bernett Lum, Josephine Zolezzi, Francesca Poidinger, Michael Rotzschke, Olaf Khor, Chiea Chuen Wilkinson, Robert J. Wang, Yee T. Chandy, George K De Libero, Gennaro Singhal, Amit Prabhakar, Shyam Nat Microbiol Article Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens. Nature Publishing Group UK 2022-01-31 2022 /pmc/articles/PMC9439955/ /pubmed/35102304 http://dx.doi.org/10.1038/s41564-021-01049-w Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article del Rosario, Ricardo C. H. Poschmann, Jeremie Lim, Carey Cheng, Catherine Y. Kumar, Pavanish Riou, Catherine Ong, Seow Theng Gerges, Sherif Hajan, Hajira Shreen Kumar, Dilip Marzuki, Mardiana Lu, Xiaohua Lee, Andrea Wijaya, Giovani Claresta Rayan, Nirmala Arul Zhuang, Zhong Du Bruyn, Elsa Chee, Cynthia Bin Eng Lee, Bernett Lum, Josephine Zolezzi, Francesca Poidinger, Michael Rotzschke, Olaf Khor, Chiea Chuen Wilkinson, Robert J. Wang, Yee T. Chandy, George K De Libero, Gennaro Singhal, Amit Prabhakar, Shyam Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title | Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title_full | Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title_fullStr | Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title_full_unstemmed | Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title_short | Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection |
title_sort | histone acetylome-wide associations in immune cells from individuals with active mycobacterium tuberculosis infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9439955/ https://www.ncbi.nlm.nih.gov/pubmed/35102304 http://dx.doi.org/10.1038/s41564-021-01049-w |
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