Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function.
Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function.
复制标题
DOI：
10.1186/gb-2013-14-8-r83
复制
发表时间：
2013-08-19
期刊：
影响因子：
12.3
通讯作者：
Ingelman-Sundberg M
中科院分区：
文献类型：
--
作者：
Ivanov M;Kals M;Kacevska M;Barragan I;Kasuga K;Rane A;Metspalu A;Milani L;Ingelman-Sundberg M
肝脏功能如蛋白质合成、脂质和碳水化合物代谢以及药物代谢的个体间差异受到表观遗传因素的影响。然而，表观遗传机制在这些过程中的作用几乎没有被研究。5-羟甲基胞嘧啶（5 hmC）是最近重新发现的表观遗传DNA修饰，其在基因表达控制中起重要作用。在这项研究中，我们研究了5 hmC的发生和基因组分布在8个胎儿和7个成人肝脏样本的个体发育和功能。LC-MS分析显示，在成人肝脏样品中，5 hmC占总胞嘧啶含量的1%，而在所有胎儿肝脏中，5 hmC低于0.125%。用多克隆抗5 hmC抗体对肝切片进行免疫组化染色，结果表明在大多数肝细胞中检测到5 hmC。通过下一代测序对人类肝脏样本中5 hmC分布的全基因组定位显示胎儿和成人肝脏之间存在显著差异。在成人肝脏中，5 hmC占据在参与活跃的分解代谢和代谢过程的基因中过度表达，而仅在胎儿肝脏中发现并在成人状态下消失的5 hmC元件对分化和发育途径更具特异性。我们的研究结果表明，5-羟甲基胞嘧啶在人类肝脏的发育和功能中起着重要作用，可能是肝脏疾病发展以及药物代谢和毒性个体间差异的重要决定因素。
Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression. In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development. Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity.
登录
查看更多内容
影响因子：
14.9
作者：
Sérandour AA;Avner S;Oger F;Bizot M;Percevault F;Lucchetti-Miganeh C;Palierne G;Gheeraert C;Barloy-Hubler F;Péron CL;Madigou T;Durand E;Froguel P;Staels B;Lefebvre P;Métivier R;Eeckhoute J;Salbert G
通讯作者：
Salbert G
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：
6.4
作者：
Kraus, Theo F. J.;Globisch, Daniel;Kretzschmar, Hans A.
通讯作者：
Kretzschmar, Hans A.
影响因子：
14.9
作者：
Jin SG;Wu X;Li AX;Pfeifer GP
通讯作者：
Pfeifer GP
影响因子：
10.3
作者：
Reitman, Zachary J.;Yan, Hai
通讯作者：
Yan, Hai