Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection.
Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection.
复制标题
DOI：
10.1038/s41564-021-01049-w
复制
发表时间：
2022-03
影响因子：
28.3
通讯作者：
中科院分区：
文献类型：
--
作者：
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. 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.
登录
查看更多内容
影响因子：
7.3
作者：
Donovan ML;Schultz TE;Duke TJ;Blumenthal A
通讯作者：
Blumenthal A
影响因子：
4.5
作者：
Festen EA;Goyette P;Green T;Boucher G;Beauchamp C;Trynka G;Dubois PC;Lagacé C;Stokkers PC;Hommes DW;Barisani D;Palmieri O;Annese V;van Heel DA;Weersma RK;Daly MJ;Wijmenga C;Rioux JD
通讯作者：
Rioux JD
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.8
作者：
通讯作者：
--