CpG methylation of a silent controlling element in the murine Avy allele is incomplete and unresponsive to methyl donor supplementation.
CpG methylation of a silent controlling element in the murine Avy allele is incomplete and unresponsive to methyl donor supplementation.
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DOI：
10.1371/journal.pone.0009055
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发表时间：
2010-02-04
期刊：
影响因子：
3.7
通讯作者：
Martin DI
中科院分区：
文献类型：
--
作者：
Cropley JE;Suter CM;Beckman KB;Martin DI
刺鼠 (Avy) 的活性黄色等位基因因其不稳定且部分可遗传的表观遗传状态而引人注目，这会导致同基因小鼠的表型发生广泛变化。在 Avy 等位基因中，插入的脑池内 A 颗粒（IAP）充当控制元件，通过从 IAP 的 LTR 转录来解除刺鼠表达的调节；表型状态与 LTR 的 CpG 甲基化有关。 Avy 小鼠之间的表型变异表明 IAP 的表观遗传状态在种系中不稳定。我们使用亚硫酸氢盐等位基因测序对IAP的体细胞甲基化进行了详细检查，发现启动子即使在转录沉默时也不完全甲基化。在子宫内暴露于补充甲基供体会改变 Avy 表型谱，但不会增加沉默 LTR 中 CpG 甲基化的密度。我们的研究结果表明，与之前的假设相反，甲基供体补充通过间接机制发挥沉默 Avy 的作用。我们在体细胞沉默 Avy 等位基因上观察到的不完全胞嘧啶甲基化可能反映了其不稳定的种系状态，以及 CpG 甲基化背后的表观遗传修饰的影响。
The viable yellow allele of agouti (Avy) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the Avy allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between Avy mice indicates that the epigenetic state of the IAP is unstable in the germline. We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of Avy phenotypes, does not increase the density of CpG methylation in the silent LTR. Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence Avy. The incomplete cytosine methylation we observe at the somatically silent Avy allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying CpG methylation.
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影响因子：
30.8
作者：
Suter, CM;Martin, DIK;Ward, RL
通讯作者：
Ward, RL
影响因子：
3.1
作者：
DICKIES, MM
通讯作者：
DICKIES, MM
影响因子：
4
作者：
Smit, AFA
通讯作者：
Smit, AFA
影响因子：
4
作者：
PERRY, WL;COPELAND, NG;JENKINS, NA
通讯作者：
JENKINS, NA
在小鼠表观遗传敏感等位基因上DNA甲基化的动态重编程。
影响因子：
4.5
作者：
Blewitt ME;Vickaryous NK;Paldi A;Koseki H;Whitelaw E
通讯作者：
Whitelaw E