Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.
Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.
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DOI：
10.1038/srep06263
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发表时间：
2014-09-02
影响因子：
4.6
通讯作者：
Yagi T
中科院分区：
文献类型：
--
作者：
Kaneko R;Abe M;Hirabayashi T;Uchimura A;Sakimura K;Yanagawa Y;Yagi T
串联重复在整个脊椎动物进化过程中集中在Pcdh簇内，并作为人类群体中的拷贝数变异（CNVs），但Pcdh簇中串联重复的影响仍然难以捉摸。为了研究Pcdh簇中串联重复的影响，在这里，我们产生并分析了一个新的Pcdh簇突变小鼠系。在突变等位基因中，含有Pcdh-α2至Pcdh-αc2可变外显子及其启动子的218 kb区域被复制，并可区分出单个复制的Pcdh亚型。Pcdh-α异构体具有相同的启动子序列，但其表达水平差异较大，表达方式为随机表达。有趣的是，在野生型脑中组成性表达的5′-定位重复Pcdh-αc2转变为随机表达，伴随着DNA甲基化的增加。这些结果表明，串联重复的Pcdh集群扩展的随机表达谱，而不管序列的分歧。
Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-α2 to Pcdh-αc2 variable exons with their promoters was duplicated and the individual duplicated Pcdh isoforms can be disctinguished. The individual duplicated Pcdh-α isoforms showed diverse expression level with stochastic expression manner, even though those have an identical promoter sequence. Interestingly, the 5′-located duplicated Pcdh-αc2, which is constitutively expressed in the wild-type brain, shifted to stochastic expression accompanied by increased DNA methylation. These results demonstrate that tandem duplication in the Pcdh cluster expands the stochastic expression repertoire irrespective of sequence divergence.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
影响因子：
4.8
作者：
Hirano K;Kaneko R;Izawa T;Kawaguchi M;Kitsukawa T;Yagi T
通讯作者：
Yagi T
影响因子：
3.7
作者：
Jiang XJ;Li S;Ravi V;Venkatesh B;Yu WP
通讯作者：
Yu WP
影响因子：
64.5
作者：
Fuss, Stefan H.;Omura, Masayo;Mombaerts, Peter
通讯作者：
Mombaerts, Peter
影响因子：
4.8
作者：
Kawaguchi, Masahumi;Toyama, Tomoko;Yagi, Takeshi
通讯作者：
Yagi, Takeshi