当前位置: X-MOL 学术Epigenetics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation
Epigenetics ( IF 3.7 ) Pub Date : 2020-10-24 , DOI: 10.1080/15592294.2020.1834919
Mayur Doke 1 , Venkatesh Jeganathan 2 , Jay P McLaughlin 3 , Thangavel Samikkannu 1
Affiliation  

ABSTRACT

Human immunodeficiency virus (HIV) infection and the psychostimulant drug cocaine are known to induce epigenetic changes in DNA methylation that are linked with the severity of viral replication and disease progression, which impair neuronal functions. Increasing evidence suggests that changes in DNA methylation and hydroxymethylation occur in mitochondrial DNA (mtDNA) and represent mitochondrial genome epigenetic modifications (mitoepigenetic modifications). These modifications likely regulate both mtDNA replication and gene expression. However, mtDNA methylation has not been studied extensively in the contexts of cocaine abuse and HIV-1 infection. In the present study, epigenetic factors changed the levels of the DNA methyltransferases (DNMTs) DNMT1, DNMT3a, and DNMT3b, the Ten-eleven translocation (TET) enzymes 1, 2, and 3, and mitochondrial DNMTs (mtDNMTs) both in vitro and in vivo. These changes resulted in alterations in mtDNA methylation levels at CpG and non-CpG sites in human primary astrocytes as measured using targeted next-generation bisulphite sequencing (TNGBS). Moreover, mitochondrial methylation levels in the MT-RNR1, MT-ND5, MT-ND1, D-loop and MT-CYB regions of mtDNA were lower in the HIV-1 Tat and cocaine treatment groups than in the control group. In summary, the present findings suggest that mitoepigenetic modification in the human brain causes the mitochondrial dysfunction that gives rise to neuro-AIDS.



中文翻译:

HIV-1 Tat 和可卡因影响线粒体表观遗传学:对 DNA 甲基化的影响

摘要

已知人类免疫缺陷病毒 (HIV) 感染和精神兴奋药物可卡因会诱导 DNA 甲基化的表观遗传变化,这些变化与病毒复制的严重程度和疾病进展有关,从而损害神经元功能。越来越多的证据表明,DNA 甲基化和羟甲基化的变化发生在线粒体 DNA (mtDNA) 中,代表了线粒体基因组表观遗传修饰(mitoepigenetic modified)。这些修饰可能同时调节 mtDNA 复制和基因表达。然而,在可卡因滥用和 HIV-1 感染的情况下,尚未对 mtDNA 甲基化进行广泛研究。在本研究中,表观遗传因素改变了 DNA 甲基转移酶 (DNMTs) DNMT1、DNMT3a 和 DNMT3b、10-11 易位 (TET) 酶 1、2 和 3 的水平,体外体内。这些变化导致人类原代星形胶质细胞中 CpG 和非 CpG 位点的 mtDNA 甲基化水平发生变化,这是使用靶向下一代亚硫酸氢盐测序 (TNGBS) 测量的。此外,在 HIV-1 Tat 和可卡因治疗组中,mtDNA 的 MT-RNR1、MT-ND5、MT-ND1、D-loop 和 MT-CYB 区域的线粒体甲基化水平低于对照组。总之,目前的研究结果表明,人脑中的线粒体表观遗传修饰会导致线粒体功能障碍,从而导致神经艾滋病。

更新日期:2020-10-24
down
wechat
bug