Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene
Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene
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DOI：
10.1016/j.gene.2008.11.019
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发表时间：
2009-03-01
期刊：
影响因子：
3.5
通讯作者：
Kishino, Tatsuya
中科院分区：
文献类型：
--
作者：
Miyazaki, Kazumi;Mapendano, Christophe K.;Kishino, Tatsuya
小鼠Snurf/Snrpn基因有两个差异甲基化区（DMRs），母系在5‘端甲基化区（DMR1）和父系在3’端甲基化区（DMR2）。DMR1，一个包含Snrpn启动子和整个内含子1的区域，被认为是一个种系DMR，它从配子中继承了亲本特异性甲基化谱。DMR1不仅与印迹Snrpn表达相关，还与该区域其他基因的印迹控制有关。我们现在已经在人类和啮齿类动物中鉴定了Snrpn内含子1中高度保守的激活子序列（CAS），并证明小鼠CAS不是种系DMR，但显示出DNA甲基化的发育动态变化，并具有甲基化敏感增强子活性。小鼠CAS的组织特异性甲基化及其甲基化敏感增强子活性可能控制IC转录本的组织特异性表达，导致Snrpn位点印迹的建立和/或维持。(c) 2008 Elsevier B.V.版权所有
The mouse Snurf/Snrpn gene has two differentially methylated regions (DMRs), the maternally methylated region at the 5' end (DMR1) and the paternally methylated region at the 3' end (DMR2). DMR1, a region that includes the Snrpn promoter and the entire intron 1, has been thought to be a germline DMR, which inherits the parental-specific methylation profile from the gametes. DMR1 is not only associated with imprinted Snrpn expression, but implicated in imprinting control of other genes in the region. We have now characterized the highly conserved activator sequence (CAS) in the Snrpn intron 1 among human and rodents and demonstrate that the mouse CAS is not a germline DMR but shows developmentally dynamic changes of DNA methylation and has methylation-sensitive enhancer activity. The tissue-specific methylation of the mouse CAS and its methylation-sensitive enhancer activity may control tissue-specific expression of IC transcripts, resulting in the establishment and/or maintenance of imprinting in the Snrpn locus. (c) 2008 Elsevier B.V. All rights reserved.