The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern.
The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern.
复制标题
DOI：
10.1093/dnares/dst029
复制
发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Passarino G
中科院分区：
文献类型：
--
作者：
Bellizzi D;D'Aquila P;Scafone T;Giordano M;Riso V;Riccio A;Passarino G
DNA甲基化是哺乳动物基因组常见的表观遗传修饰。关于线粒体DNA（mtDNA）中可能存在甲基化胞嘧啶的证据已经有报道。为了阐明这一点，我们分析了mtDNA控制区（D-环）的甲基化状态的人和小鼠的血液和培养细胞的DNA样品，亚硫酸氢盐测序和甲基化/羟甲基化DNA免疫沉淀试验。我们发现甲基化和羟甲基化胞嘧啶的L-链的所有样品进行了分析。mtDNA甲基化特别发生在非C-磷酸-G（非CpG）核苷酸内，主要在重链的启动子区域和保守序列块中，表明其参与调节mtDNA复制和/或转录。我们观察到线粒体内的DNA甲基转移酶，但小鼠胚胎干细胞（ES）中Dnmt 1，Dnmt 3a和Dnmt 3b的失活导致CpG甲基化减少，而非CpG甲基化显示不受影响。这表明D环表观遗传修饰仅部分由这些酶建立。我们的数据表明，DNA甲基化发生在哺乳动物的mtDNA控制区，不仅在对称的CpG二核苷酸，典型的核基因组，但在一个特殊的非CpG模式以前报道的植物和真菌。负责这种模式的分子机制仍然是一个悬而未决的问题。
DNA methylation is a common epigenetic modification of the mammalian genome. Conflicting data regarding the possible presence of methylated cytosines within mitochondrial DNA (mtDNA) have been reported. To clarify this point, we analysed the methylation status of mtDNA control region (D-loop) on human and murine DNA samples from blood and cultured cells by bisulphite sequencing and methylated/hydroxymethylated DNA immunoprecipitation assays. We found methylated and hydroxymethylated cytosines in the L-strand of all samples analysed. MtDNA methylation particularly occurs within non-C-phosphate-G (non-CpG) nucleotides, mainly in the promoter region of the heavy strand and in conserved sequence blocks, suggesting its involvement in regulating mtDNA replication and/or transcription. We observed DNA methyltransferases within the mitochondria, but the inactivation of Dnmt1, Dnmt3a, and Dnmt3b in mouse embryonic stem (ES) cells results in a reduction of the CpG methylation, while the non-CpG methylation shows to be not affected. This suggests that D-loop epigenetic modification is only partially established by these enzymes. Our data show that DNA methylation occurs in the mtDNA control region of mammals, not only at symmetrical CpG dinucleotides, typical of nuclear genome, but in a peculiar non-CpG pattern previously reported for plants and fungi. The molecular mechanisms responsible for this pattern remain an open question.
登录
查看更多内容
影响因子：
3.5
作者：
Park J;Xu K;Park T;Yi SV
通讯作者：
Yi SV
影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
4.2
作者：
Fuso, Andrea;Nicolia, Vincenzina;Scarpa, Sigfrido
通讯作者：
Scarpa, Sigfrido
DOI：
10.1016/0005-2787(79)90233-8
发表时间：
1979-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GROOT, GSP;KROON, AM
通讯作者：
KROON, AM