DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns.
DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns.
复制标题
DOI：
10.1186/gb-2014-15-4-r54
复制
发表时间：
2014-04-01
期刊：
影响因子：
12.3
通讯作者：
Tõnisson N
中科院分区：
文献类型：
--
作者：
Lokk K;Modhukur V;Rajashekar B;Märtens K;Mägi R;Kolde R;Koltšina M;Nilsson TK;Vilo J;Salumets A;Tõnisson N
DNA表观遗传修饰，如甲基化，是组织分化的重要调节因子，有助于发育和癌症的过程。分析组织特异性DNA甲基化模式将为正常和致病机制提供新的见解，并有助于未来的表观遗传治疗。在这项研究中，17个体细胞组织从四个尸检的人进行功能基因组分析，使用Illumina Infinium HumanMethylation 450珠芯片，覆盖486 428个CpG位点。在所有17个组织样本中，只有2%的CpG分析是高甲基化的，这些永久甲基化的CpG位点主要位于基因体区域。相比之下，15%的CpG是低甲基化在所有标本中，主要位于转录起始位点附近的区域。大量的组织特异性差异甲基化区域被鉴定并被认为是组织特异性基因调控机制的可能介质，因为低甲基化区域与相应组织的已知功能密切相关。最后，在CpG岛内的启动子甲基化和从公开数据库获得的基因表达数据之间观察到明显的负相关。这项全基因组甲基化分析研究在17个人体组织中鉴定了组织特异性差异甲基化区域。与这些差异甲基化区域相对应的许多基因有助于组织特异性功能。未来的研究可能会使用这些数据作为参考，以确定扰动分化和疾病相关的致病机制的标志物。
DNA epigenetic modifications, such as methylation, are important regulators of tissue differentiation, contributing to processes of both development and cancer. Profiling the tissue-specific DNA methylome patterns will provide novel insights into normal and pathogenic mechanisms, as well as help in future epigenetic therapies. In this study, 17 somatic tissues from four autopsied humans were subjected to functional genome analysis using the Illumina Infinium HumanMethylation450 BeadChip, covering 486 428 CpG sites. Only 2% of the CpGs analyzed are hypermethylated in all 17 tissue specimens; these permanently methylated CpG sites are located predominantly in gene-body regions. In contrast, 15% of the CpGs are hypomethylated in all specimens and are primarily located in regions proximal to transcription start sites. A vast number of tissue-specific differentially methylated regions are identified and considered likely mediators of tissue-specific gene regulatory mechanisms since the hypomethylated regions are closely related to known functions of the corresponding tissue. Finally, a clear inverse correlation is observed between promoter methylation within CpG islands and gene expression data obtained from publicly available databases. This genome-wide methylation profiling study identified tissue-specific differentially methylated regions in 17 human somatic tissues. Many of the genes corresponding to these differentially methylated regions contribute to tissue-specific functions. Future studies may use these data as a reference to identify markers of perturbed differentiation and disease-related pathogenic mechanisms.
登录
查看更多内容
影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
DOI：
10.1097/ede.0b013e31824523f0
发表时间：
2012-03
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Bind MA;Baccarelli A;Zanobetti A;Tarantini L;Suh H;Vokonas P;Schwartz J
通讯作者：
Schwartz J
影响因子：
14.9
作者：
Rustici G;Kolesnikov N;Brandizi M;Burdett T;Dylag M;Emam I;Farne A;Hastings E;Ison J;Keays M;Kurbatova N;Malone J;Mani R;Mupo A;Pedro Pereira R;Pilicheva E;Rung J;Sharma A;Tang YA;Ternent T;Tikhonov A;Welter D;Williams E;Brazma A;Parkinson H;Sarkans U
通讯作者：
Sarkans U
影响因子：
3.3
作者：
Elango, Navin;Yi, Soojin V.
通讯作者：
Yi, Soojin V.