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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
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.
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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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