Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2022-01-31
Date Acceptance
2021-12-14
Citation
Nature Microbiology, 2022, 7 (2), pp.312-326
ISSN
2058-5276
Publisher
Nature Research
Start Page
312
End Page
326
Journal / Book Title
Nature Microbiology
Volume
7
Issue
2
Copyright Statement
© The Author(s) 2022, corrected publication 2022. 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/.
License URL
Sponsor
Wellcome Trust
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000750487300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
WDAI_P83556
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
CHROMATIN STATES
K+ CHANNEL
GENE
IDENTIFICATION
MACROPHAGE
EXPRESSION
SIGNATURES
APOPTOSIS
AUTOPHAGY
VARIANTS
Publication Status
Published
Date Publish Online
2022-01-31