Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes.
Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes.
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DOI：
10.1186/s13148-015-0064-6
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发表时间：
2015
影响因子：
5.7
通讯作者：
Kere J
中科院分区：
文献类型：
--
作者：
Acevedo N;Reinius LE;Vitezic M;Fortino V;Söderhäll C;Honkanen H;Veijola R;Simell O;Toppari J;Ilonen J;Knip M;Scheynius A;Hyöty H;Greco D;Kere J
儿童早期血液白细胞DNA甲基化的年龄相关变化可能反映了表观遗传成熟。我们假设其中一些变化涉及与白细胞生物学密切相关的基因网络，并进行了一项前瞻性研究，以阐明DNA甲基化的动力学。参加1型糖尿病预测和预防研究的10名在芬兰出生的健康女孩在出生后3、6、12、24、36、48和60个月采集了一系列血样。DNA甲基化检测使用的是人类甲基化450珠芯片。在筛选了多态和细胞系特异性特征后，所有儿童中有794个CpG位点显示出显著的DNA甲基化差异作为年龄的函数(41.6%的年龄甲基化和58.4%的年龄去甲基化，经Bonferroni校正的P值和0.01)。AGE甲基化的CPGS更多地位于基因体和转录起始点(TSS)的+5~+50kb(Kb)范围内，并富含发育、神经元和质膜基因。年龄去甲基化的CpG与启动子和DNA酶-I超敏位点相关，位于最近的TS的−5~+5kb范围内，富含与免疫、抗原提呈、多梳蛋白复合体和细胞质相关的基因。这项研究揭示了复杂炎症性疾病的易感基因(例如IRF5、NOD2和PTGER4)以及编码组蛋白修饰物和染色质重塑因子的基因(例如HDAC4、KDM2a、Kdm2b、JARID2、ARID3A和SMARCD3)在儿童早期经历了DNA甲基化的变化。这些结果为理解白细胞成熟开辟了新的视角，并提供了在进行儿童DNA甲基化研究时可能需要校正年龄效应的CpG位点目录。本文的在线版本(doi：10.1186/s13148.0150064-6)包含补充材料，授权用户可以使用。
Age-related changes in DNA methylation occurring in blood leukocytes during early childhood may reflect epigenetic maturation. We hypothesized that some of these changes involve gene networks of critical relevance in leukocyte biology and conducted a prospective study to elucidate the dynamics of DNA methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60 months after birth in ten healthy girls born in Finland and participating in the Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured using the HumanMethylation450 BeadChip. After filtering for the presence of polymorphisms and cell-lineage-specific signatures, 794 CpG sites showed significant DNA methylation differences as a function of age in all children (41.6% age-methylated and 58.4% age-demethylated, Bonferroni-corrected P value <0.01). Age-methylated CpGs were more frequently located in gene bodies and within +5 to +50 kilobases (kb) of transcription start sites (TSS) and enriched in developmental, neuronal and plasma membrane genes. Age-demethylated CpGs were associated to promoters and DNAse-I hypersensitivity sites, located within −5 to +5 kb of the nearest TSS and enriched in genes related to immunity, antigen presentation, the polycomb-group protein complex and cytoplasm. This study reveals that susceptibility loci for complex inflammatory diseases (for example, IRF5, NOD2, and PTGER4) and genes encoding histone modifiers and chromatin remodeling factors (for example, HDAC4, KDM2A, KDM2B, JARID2, ARID3A, and SMARCD3) undergo DNA methylation changes in leukocytes during early childhood. These results open new perspectives to understand leukocyte maturation and provide a catalogue of CpG sites that may need to be corrected for age effects when performing DNA methylation studies in children. The online version of this article (doi:10.1186/s13148-015-0064-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
16.2
作者：
Kukko, M;Virtanen, SM;Knip, M
通讯作者：
Knip, M