Age-specific changes in genome-wide methylation enrich for Foxa2 and estrogen receptor alpha binding sites.
Age-specific changes in genome-wide methylation enrich for Foxa2 and estrogen receptor alpha binding sites.
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DOI：
10.1371/journal.pone.0203147
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Druley TE
中科院分区：
文献类型：
--
作者：
Uli N;Michelen-Gomez E;Ramos EI;Druley TE
DNA 甲基化模式在复杂表型中的作用仍不清楚。为了探索这个问题，我们采用了罕见变异分析方法来表征全基因组小鼠 DNA 杂交阵列，以研究 CpG 岛、海岸和调控元件的甲基化。我们应用这个平台来比较年轻和老年小鼠大脑和脾脏的年龄和组织特异性甲基化差异。正如之前研究所预期的那样，器官特异性甲基化存在明显的全球差异，但年龄特异性甲基化不存在明显的差异，这主要是由于重复元件的变化。令人惊讶的是，在 200,000 个位点中，年轻和年老样本之间只有 946 个差异甲基化胞嘧啶 (DMC)（老年小鼠中有 529 个高甲基化，417 个低甲基化），而组织特异性的 DMC 有数千个。高甲基化位点聚集在 Sfi1 的启动子区域、Slc11a2 的外显子 2、Drg1、Esr1 和 Foxa2 转录因子结合位点周围。特别是，11 号染色体 2.7 Mb 区域有 75 个高甲基化 Foxa2 结合位点。低甲基化位点聚集在 Mid1、Isoc2b 和全基因组位点周围，这些位点具有 Foxa2 和 Esr1 的结合位点，已知这些位点在发育和衰老中发挥重要作用。这些数据表明，与细胞分裂（Sfi1、Mid1）、能量产生（Drg1、Isoc2b）和细胞死亡（Foxa2、Esr1）等衰老过程相关的、与组织无关的甲基化变化。
The role of DNA methylation patterns in complex phenotypes remains unclear. To explore this question, we adapted our methods for rare variant analysis to characterize genome-wide murine DNA hybridization array to investigate methylation at CpG islands, shores, and regulatory elements. We have applied this platform to compare age and tissue- specific methylation differences in the brain and spleen of young and aged mice. As expected from prior studies, there are clear global differences in organ-specific, but not age-specific, methylation due mostly to changes at repetitive elements. Surprisingly, out of 200,000 loci there were only 946 differentially methylated cytosines (DMCs) between young and old samples (529 hypermethylated, 417 hypomethylated in aged mice) compared to thousands of tissue-specific DMCs. Hypermethylated loci were clustered around the promoter region of Sfi1, exon 2 of Slc11a2, Drg1, Esr1 and Foxa2 transcription factor binding sites. In particular, there were 75 hypermethylated Foxa2 binding sites across a 2.7 Mb region of chromosome 11. Hypomethylated loci were clustered around Mid1, Isoc2b and genome-wide loci with binding sites for Foxa2 and Esr1, which are known to play important roles in development and aging. These data suggest discreet tissue-independent methylation changes associated with aging processes such as cell division (Sfi1, Mid1), energy production (Drg1, Isoc2b) and cell death (Foxa2, Esr1).
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影响因子：
4
作者：
Kaestner, Klaus H.
通讯作者：
Kaestner, Klaus H.
影响因子：
11
作者：
Ladd-Acosta, C.;Hansen, K. D.;Briem, E.;Fallin, M. D.;Kaufmann, W. E.;Feinberg, A. P.
通讯作者：
Feinberg, A. P.
影响因子：
7.8
作者：
Jones MJ;Goodman SJ;Kobor MS
通讯作者：
Kobor MS
影响因子：
4.8
作者：
Carrió E;Suelves M
通讯作者：
Suelves M
影响因子：
4.8
作者：
Levenson, Jonathan M.;Roth, Tania L.;Sweatt, J. David
通讯作者：
Sweatt, J. David