Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{del:2022:10.1038/s41564-021-01049-w,
author = {del, Rosario RCH and Poschmann, J and Lim, C and Cheng, CY and Kumar, P and Riou, C and Ong, ST and Gerges, S and Hajan, HS and Kumar, D and Marzuki, M and Lu, X and Lee, A and Wijaya, GC and Rayan, NA and Zhuang, Z and Du, Bruyn E and Chee, CBE and Lee, B and Lum, J and Zolezzi, F and Poidinger, M and Rotzschke, O and Khor, CC and Wilkinson, RJ and Wang, YT and Chandy, GK and De, Libero G and Singhal, A and Prabhakar, S},
doi = {10.1038/s41564-021-01049-w},
journal = {Nature Microbiology},
pages = {312--326},
title = {Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection},
url = {http://dx.doi.org/10.1038/s41564-021-01049-w},
volume = {7},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - del,Rosario RCH
AU  - Poschmann,J
AU  - Lim,C
AU  - Cheng,CY
AU  - Kumar,P
AU  - Riou,C
AU  - Ong,ST
AU  - Gerges,S
AU  - Hajan,HS
AU  - Kumar,D
AU  - Marzuki,M
AU  - Lu,X
AU  - Lee,A
AU  - Wijaya,GC
AU  - Rayan,NA
AU  - Zhuang,Z
AU  - Du,Bruyn E
AU  - Chee,CBE
AU  - Lee,B
AU  - Lum,J
AU  - Zolezzi,F
AU  - Poidinger,M
AU  - Rotzschke,O
AU  - Khor,CC
AU  - Wilkinson,RJ
AU  - Wang,YT
AU  - Chandy,GK
AU  - De,Libero G
AU  - Singhal,A
AU  - Prabhakar,S
DO  - 10.1038/s41564-021-01049-w
EP  - 326
PY  - 2022///
SN  - 2058-5276
SP  - 312
TI  - Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection
T2  - Nature Microbiology
UR  - http://dx.doi.org/10.1038/s41564-021-01049-w
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000750487300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41564-021-01049-w
UR  - http://hdl.handle.net/10044/1/100588
VL  - 7
ER  -
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