Phylogenetic and DNA methylation analysis reveal novel regions of variable methylation in the mouse IAP class of transposons
Phylogenetic and DNA methylation analysis reveal novel regions of variable methylation in the mouse IAP class of transposons
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DOI：
10.1186/1471-2164-14-48
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发表时间：
2013-01-23
期刊：
影响因子：
4.4
通讯作者：
Dolinoy, Dana C.
中科院分区：
文献类型：
--
作者：
Faulk, Christopher;Barks, Amanda;Dolinoy, Dana C.
背景资料：在长末端重复序列（LTR）类中选择反转录转座子表现出DNA甲基化的个体间变异，这种变异会因发育环境暴露而改变。然而，无论是在这些“亚稳态表观等位基因”的变异性的全部范围，也不是潜在的变量元件的系统发育关系是很好地理解。小鼠亚稳态表观等位基因，A（vy）和Cabp（IAP），结果从独立插入的脑池内A颗粒（IAP）移动的元件，并表现出显着相似的序列同一性（98.5%）。结果：利用C57 BL/6基因组，我们确定了10802 IAP LTR的整体和一个子集的1388个家庭，包括A（vy）和Cabp（IAP）。系统发育分析显示，两个重复和分歧事件细分为三个分支这个家庭。为了表征跨进化枝的个体间变异，对来自17只同基因小鼠的肝脏DNA进行21个单独的LTR转座子（每个进化枝7个）的亚硫酸氢盐和限制性内切酶分析（CoBRA）。最低和最高平均甲基化值分别为59%和88%，而单个LTR的甲基化水平变化很大，范围从9%到34%。具有最保守元件的进化枝在LTR中具有比两个分歧进化枝中的任一个显著更高的平均甲基化（p = 0.040和p = 0.017）。在每只小鼠中，所有LTR的平均甲基化没有显著差异（71%-74%，p > 0.99）。结论：结合系统发育和DNA甲基化分析可以识别新的可变甲基化区域。这种方法增加了小鼠中已知的亚稳态表观等位基因的数量，这些表观等位基因可以作为表观基因组环境修饰的生物标志物。
Background: Select retrotransposons in the long terminal repeat (LTR) class exhibit interindividual variation in DNA methylation that is altered by developmental environmental exposures. Yet, neither the full extent of variability at these "metastable epialleles," nor the phylogenetic relationship underlying variable elements is well understood. The murine metastable epialleles, A(vy) and Cabp(IAP), result from independent insertions of an intracisternal A particle (IAP) mobile element, and exhibit remarkably similar sequence identity (98.5%).Results: Utilizing the C57BL/6 genome we identified 10802 IAP LTRs overall and a subset of 1388 in a family that includes A(vy) and Cabp(IAP). Phylogenetic analysis revealed two duplication and divergence events subdividing this family into three clades. To characterize interindividual variation across clades, liver DNA from 17 isogenic mice was subjected to combined bisulfite and restriction analysis (CoBRA) for 21 separate LTR transposons (7 per clade). The lowest and highest mean methylation values were 59% and 88% respectively, while methylation levels at individual LTRs varied widely, ranging from 9% to 34%. The clade with the most conserved elements had significantly higher mean methylation across LTRs than either of the two diverged clades (p = 0.040 and p = 0.017). Within each mouse, average methylation across all LTRs was not significantly different (71% 74%, p > 0.99).Conclusions: Combined phylogenetic and DNA methylation analysis allows for the identification of novel regions of variable methylation. This approach increases the number of known metastable epialleles in the mouse, which can serve as biomarkers for environmental modifications to the epigenome.