Sharma Garima, Sowpati Divya Tej, Singh Prakruti, Khan Mehak Zahoor, Ganji Rakesh, Upadhyay Sandeep, Banerjee Sharmistha, Nandicoori Vinay Kumar, Khosla Sanjeev
Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India.
Graduate Studies, Manipal University, Manipal 576104, India.
Sci Rep. 2016 Apr 26;6:25006. doi: 10.1038/srep25006.
A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative conditions and cardiovascular diseases have been documented. Here we show genome-wide DNA methylation changes in macrophages infected with the pathogen M. tuberculosis. Majority of the affected genomic loci were hypermethylated in M. tuberculosis infected THP1 macrophages. Hotspots of differential DNA methylation were enriched in genes involved in immune response and chromatin reorganization. Importantly, DNA methylation changes were observed predominantly for cytosines present in non-CpG dinucleotide context. This observation was consistent with our previous finding that the mycobacterial DNA methyltransferase, Rv2966c, targets non-CpG dinucleotides in the host DNA during M. tuberculosis infection and reiterates the hypothesis that pathogenic bacteria use non-canonical epigenetic strategies during infection.
哺乳动物细胞利用DNA甲基化来调节基因表达，以应对发育和分化过程中的环境变化。与癌症、神经退行性疾病和心血管疾病等疾病状态相关的异常DNA甲基化变化已有文献记载。在此，我们展示了感染病原体结核分枝杆菌的巨噬细胞中全基因组DNA甲基化的变化。在结核分枝杆菌感染的THP1巨噬细胞中，大多数受影响的基因组位点发生了高甲基化。差异DNA甲基化的热点区域富含参与免疫反应和染色质重组的基因。重要的是，主要在非CpG二核苷酸背景下的胞嘧啶中观察到了DNA甲基化变化。这一观察结果与我们之前的发现一致，即在结核分枝杆菌感染期间，分枝杆菌DNA甲基转移酶Rv2966c靶向宿主DNA中的非CpG二核苷酸，并重申了病原菌在感染期间使用非经典表观遗传策略的假设。
