Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus.
Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus.
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印记 Herc3/Nap1l5 位点替代 mRNA 加工的表观遗传控制。
DOI：
10.1093/nar/gks654
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发表时间：
2012-10
影响因子：
14.9
通讯作者：
Oakey RJ
中科院分区：
文献类型：
--
作者：
Cowley M;Wood AJ;Böhm S;Schulz R;Oakey RJ
替代多腺苷酸化通过从单个基因产生多个转录亚型来增加转录组多样性。人们认为这一过程可能受到表观遗传调控，但鲜有报道这方面的具体例子。我们之前表明，Mcts2/H13 基因座受到基因组印记的影响，并且 H13 转录本的选择性多腺苷酸化以等位基因特异性方式发生，并受表观遗传机制的调节。在这里，我们证明等位基因特异性多聚腺苷酸化发生在具有相似特征的另一个印记基因座上。 Nap1l5 是从父系遗传等位基因表达的逆转录基因，位于“宿主”基因 Herc3 的内含子内，并与亲本等位基因之间差异甲基化的 CpG 岛重叠。在小鼠大脑中，Nap1l5 上游的内部 Herc3 多腺苷酸化位点用于表达 Nap1l5 的父本染色体上，而下游位点则更频繁地用于母本衍生染色体上。消除 Nap1l5 启动子处母体等位基因上的 DNA 甲基化会增加内部 Herc3 聚腺苷酸化位点的使用并改变外显子剪接。这些变化证明了表观遗传机制对调节 Herc3 替代 mRNA 加工的影响。 Herc3 内部多聚腺苷酸化与 Nap1l5 的表达水平相关，表明转录干扰可能发挥作用。类似的机制可能会调节基因组其他地方的选择性多聚腺苷酸化。
Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene. It is thought that this process can be subject to epigenetic regulation, but few specific examples of this have been reported. We previously showed that the Mcts2/H13 locus is subject to genomic imprinting and that alternative polyadenylation of H13 transcripts occurs in an allele-specific manner, regulated by epigenetic mechanisms. Here, we demonstrate that allele-specific polyadenylation occurs at another imprinted locus with similar features. Nap1l5 is a retrogene expressed from the paternally inherited allele, is situated within an intron of a ‘host’ gene Herc3, and overlaps a CpG island that is differentially methylated between the parental alleles. In mouse brain, internal Herc3 polyadenylation sites upstream of Nap1l5 are used on the paternally derived chromosome, from which Nap1l5 is expressed, whereas a downstream site is used more frequently on the maternally derived chromosome. Ablating DNA methylation on the maternal allele at the Nap1l5 promoter increases the use of an internal Herc3 polyadenylation site and alters exon splicing. These changes demonstrate the influence of epigenetic mechanisms in regulating Herc3 alternative mRNA processing. Internal Herc3 polyadenylation correlates with expression levels of Nap1l5, suggesting a possible role for transcriptional interference. Similar mechanisms may regulate alternative polyadenylation elsewhere in the genome.
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影响因子：
3.7
作者：
Cowley M;de Burca A;McCole RB;Chahal M;Saadat G;Oakey RJ;Schulz R
通讯作者：
Schulz R
影响因子：
14.9
作者：
Monk D;Arnaud P;Frost JM;Wood AJ;Cowley M;Martin-Trujillo A;Guillaumet-Adkins A;Iglesias Platas I;Camprubi C;Bourc'his D;Feil R;Moore GE;Oakey RJ
通讯作者：
Oakey RJ
影响因子：
1.2
作者：
Davies, W;Smith, RJ;Wilkinson, LS
通讯作者：
Wilkinson, LS
影响因子：
4.5
作者：
Kanber D;Berulava T;Ammerpohl O;Mitter D;Richter J;Siebert R;Horsthemke B;Lohmann D;Buiting K
通讯作者：
Buiting K
影响因子：
56.9
作者：
Gregg, Christopher;Zhang, Jiangwen;Dulac, Catherine
通讯作者：
Dulac, Catherine