Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection
| Autor: | Ricardo C. H. del Rosario, Jeremie Poschmann, Carey Lim, Catherine Y. Cheng, Pavanish Kumar, Catherine Riou, Seow Theng Ong, Sherif Gerges, Hajira Shreen Hajan, Dilip Kumar, Mardiana Marzuki, Xiaohua Lu, Andrea Lee, Giovani Claresta Wijaya, Nirmala Arul Rayan, Zhong Zhuang, Elsa Du Bruyn, Cynthia Bin Eng Chee, Bernett Lee, Josephine Lum, Francesca Zolezzi, Michael Poidinger, Olaf Rotzschke, Chiea Chuen Khor, Robert J. Wilkinson, Yee T. Wang, George K Chandy, Gennaro De Libero, Amit Singhal, Shyam Prabhakar |
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| Přispěvatelé: | Wellcome Trust |
| Rok vydání: | 2022 |
| Předmět: |
EXPRESSION
Adult Male Microbiology (medical) THP-1 Cells Quantitative Trait Loci Immunology VARIANTS Proof of Concept Study Applied Microbiology and Biotechnology Microbiology Monocytes Cohort Studies Histones South Africa Young Adult 1108 Medical Microbiology Genetics Humans Tuberculosis Longitudinal Studies CHROMATIN STATES SIGNATURES Genetic Association Studies Singapore Science & Technology IDENTIFICATION Acetylation Mycobacterium tuberculosis Cell Biology GENE Chromatin APOPTOSIS K+ CHANNEL AUTOPHAGY Female MACROPHAGE Life Sciences & Biomedicine Granulocytes 0605 Microbiology |
| Zdroj: | Nature Microbiology. 7:312-326 |
| ISSN: | 2058-5276 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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