Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection. del Rosario, R. C H, Poschmann, J., Lim, C., Cheng, C. Y, Kumar, P., Riou, C., Ong, S. T., Gerges, S., Hajan, H. S., Kumar, D., Marzuki, M., Lu, X., Lee, A., Wijaya, G. C., Rayan, N. A., Zhuang, Z., Du Bruyn, E., Chee, C. B. E., Lee, B., Lum, J., Zolezzi, F., Poidinger, M., Rotzschke, O., Khor, C. C., Wilkinson, R. J, Wang, Y. T, Chandy, G. K, De Libero, G., Singhal, A., & Prabhakar, S. Nature Microbiology, 7(2):312–326, Nature Publishing Group, jan, 2022. ![Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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 \textgreater2,000 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. Genome-wide histone acetylation profiling in cohorts of patients with active and latent tuberculosis reveals acetylation changes in host immune cells modulating potassium channel expression and apoptosis response.
@article{DelRosario2022,
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 {\textgreater}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. Genome-wide histone acetylation profiling in cohorts of patients with active and latent tuberculosis reveals acetylation changes in host immune cells modulating potassium channel expression and apoptosis response.},
author = {del Rosario, Ricardo C H and Poschmann, Jeremie and Lim, Carey and Cheng, Catherine Y and Kumar, Pavanish and Riou, Catherine and Ong, Seow Theng and Gerges, Sherif and Hajan, Hajira Shreen and Kumar, Dilip and Marzuki, Mardiana and Lu, Xiaohua and Lee, Andrea and Wijaya, Giovani Claresta and Rayan, Nirmala Arul and Zhuang, Zhong and {Du Bruyn}, Elsa and Chee, Cynthia Bin Eng and Lee, Bernett and Lum, Josephine and Zolezzi, Francesca and Poidinger, Michael and Rotzschke, Olaf and Khor, Chiea Chuen and Wilkinson, Robert J and Wang, Yee T and Chandy, George K and {De Libero}, Gennaro and Singhal, Amit and Prabhakar, Shyam},
doi = {10.1038/s41564-021-01049-w},
issn = {2058-5276},
journal = {Nature Microbiology},
keywords = {Functional genomics,OA,Tuberculosis,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jan},
number = {2},
pages = {312--326},
pmid = {35102304},
publisher = {Nature Publishing Group},
title = {{Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection}},
url = {https://www.nature.com/articles/s41564-021-01049-w},
volume = {7},
year = {2022}
}
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