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Article Dans Une Revue Nature Microbiology Année : 2022

Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection

Ricardo del Rosario
Carey Lim
  • Fonction : Auteur
Catherine Cheng
  • Fonction : Auteur
Pavanish Kumar
Catherine Riou
Seow Theng Ong
Sherif Gerges
  • Fonction : Auteur
Hajira Shreen Hajan
  • Fonction : Auteur
Dilip Kumar
Mardiana Marzuki
  • Fonction : Auteur
Xiaohua Lu
  • Fonction : Auteur
Andrea Lee
  • Fonction : Auteur
Giovani Claresta Wijaya
  • Fonction : Auteur
Nirmala Arul Rayan
  • Fonction : Auteur
Zhong Zhuang
  • Fonction : Auteur
Elsa Du Bruyn
  • Fonction : Auteur
Cynthia Bin Eng Chee
  • Fonction : Auteur
Bernett Lee
  • Fonction : Auteur
Josephine Lum
Francesca Zolezzi
  • Fonction : Auteur
Michael Poidinger
Olaf Rotzschke
Chiea Chuen Khor
Robert Wilkinson
  • Fonction : Auteur
Yee Wang
  • Fonction : Auteur
George Chandy
  • Fonction : Auteur
Gennaro de Libero
  • Fonction : Auteur
Amit Singhal
  • Fonction : Auteur
Shyam Prabhakar

Résumé

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.

Dates et versions

hal-03666590 , version 1 (12-05-2022)

Identifiants

Citer

Ricardo del Rosario, Jeremie Poschmann, Carey Lim, Catherine Cheng, Pavanish Kumar, et al.. Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection. Nature Microbiology, 2022, 7 (2), pp.312-326. ⟨10.1038/s41564-021-01049-w⟩. ⟨hal-03666590⟩
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