HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation.
HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation.
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DOI：
10.1080/15592294.2020.1834919
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发表时间：
2021-09
期刊：
影响因子：
3.7
通讯作者：
Samikkannu T
中科院分区：
文献类型：
--
作者：
Doke M;Jeganathan V;McLaughlin JP;Samikkannu T
人类免疫缺陷病毒(HIV)感染和精神刺激药物可卡因已知会导致DNA甲基化的表观遗传变化，这些变化与病毒复制和疾病进展的严重程度有关，从而损害神经功能。越来越多的证据表明，DNA甲基化和羟甲基化的改变发生在线粒体DNA(MtDNA)中，并代表着线粒体基因组的表观遗传修饰(mitoepigenetic修饰)。这些修饰可能同时调节线粒体DNA复制和基因表达。然而，在可卡因滥用和HIV-1感染的背景下，线粒体DNA甲基化还没有得到广泛的研究。在本研究中，表观遗传因素在体外和体内都改变了DNA甲基转移酶(DNMTs)DNMT1、DNMT3a和Dnmt3b，Tet酶1、2和3以及线粒体Dnmts(MtDNMTs)的水平。这些变化导致了人类原代星形胶质细胞中CpG和非CpG位点的mtDNA甲基化水平的变化，这是通过靶向下一代亚硫酸氢盐测序(TNGBS)测量的。此外，HIV-1Tat和可卡因治疗组线粒体DNA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。综上所述，目前的发现表明，人类大脑中的有丝分裂表观遗传修饰导致线粒体功能障碍，从而导致神经艾滋病。
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.
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影响因子：
11.4
作者：
El-Amine R;Germini D;Zakharova VV;Tsfasman T;Sheval EV;Louzada RAN;Dupuy C;Bilhou-Nabera C;Hamade A;Najjar F;Oksenhendler E;Lipinski M;Chernyak BV;Vassetzky YS
通讯作者：
Vassetzky YS
影响因子：
11.2
作者：
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通讯作者：
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影响因子：
64.8
作者：
Felsenfeld, G;Groudine, M
通讯作者：
Groudine, M
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
DOI：
10.1093/dnares/dst029
发表时间：
2013-12
期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子：
--
作者：
Bellizzi D;D'Aquila P;Scafone T;Giordano M;Riso V;Riccio A;Passarino G
通讯作者：
Passarino G