Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc.
Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc.
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DOI：
10.4161/epi.24887
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发表时间：
2013-06
期刊：
影响因子：
3.7
通讯作者：
Kono T
中科院分区：
文献类型：
--
作者：
Kobayashi H;Yanagisawa E;Sakashita A;Sugawara N;Kumakura S;Ogawa H;Akutsu H;Hata K;Nakabayashi K;Kono T
长链非编码RNA（longnoncodingRNA，lncRNA）是从动物基因组基因间区域转录而来的一类RNA，在生物学过程中起着重要作用。在小鼠中，Zdbf 2linc最近被鉴定为父本表达的印迹Zdbf 2基因的lncRNA同种型。Zdbf 2linc的功能作用尚未确定，但它可能通过顺式表观遗传修饰控制蛋白质编码邻居的亲本特异性表达，类似于印迹的Nespas，Kcnq 1 ot 1和Airn lncRNA。在这里，我们确定了一种新的印迹远程非编码RNA，称为GPR 1AS，在人类GPR 1-ZDBF 2基因间区域。虽然GPR 1AS不含人ZDBF 2外显子，但该lncRNA以反义方向从GPR 1内含子转录至ZDBF 2基因上游的二级差异甲基化区域（ZDBF 2 DMR），与小鼠Zdbf 2linc相似。有趣的是，GPR 1AS/Zdbf 2linc仅在人/小鼠胎盘中表达，具有父系等位基因特异性表达和母系等位基因特异性启动子甲基化（GPR 1/Gpr 1 DMR）。在人胎盘以及体细胞谱系中建立了二级ZDBF 2 DMR的父系等位基因特异性甲基化。同时，ZDBF 2基因在胎盘组织中表现出随机的父系等位基因特异性表达，可能是甲基化无关的。总之，我们证明了在印迹GPR 1-GPR 1AS-ZDBF 2区域中的表观遗传调节机制在人类和小鼠基因组之间是非常保守的，而没有基因间lncRNA的高度序列保守性。我们的研究结果还表明，具有高度保守的表观遗传和转录调控跨物种的lncRNA产生的分歧进化从一个共同的祖先，如果他们没有相同的外显子结构。
Long non-coding RNAs (lncRNAs), transcribed from the intergenic regions of animal genomes, play important roles in key biological processes. In mice, Zdbf2linc was recently identified as an lncRNA isoform of the paternally expressed imprinted Zdbf2 gene. The functional role of Zdbf2linc remains undefined, but it may control parent-of-origin-specific expression of protein-coding neighbors through epigenetic modification in cis, similar to imprinted Nespas, Kcnq1ot1 and Airn lncRNAs. Here, we identified a novel imprinted long-range non-coding RNA, termed GPR1AS, in the human GPR1-ZDBF2 intergenic region. Although GPR1AS contains no human ZDBF2 exons, this lncRNA is transcribed in the antisense orientation from the GPR1 intron to a secondary, differentially methylated region upstream of the ZDBF2 gene (ZDBF2 DMR), similar to mouse Zdbf2linc. Interestingly, GPR1AS/Zdbf2linc is exclusively expressed in human/mouse placenta with paternal-allele-specific expression and maternal-allele-specific promoter methylation (GPR1/Gpr1 DMR). The paternal-allele specific methylation of the secondary ZDBF2 DMR was established in human placentas as well as somatic lineage. Meanwhile, the ZDBF2 gene showed stochastic paternal-allele-specific expression, possibly methylation-independent, in placental tissues. Overall, we demonstrated that epigenetic regulation mechanisms in the imprinted GPR1-GPR1AS-ZDBF2 region were well-conserved between human and mouse genomes without the high sequence conservation of the intergenic lncRNAs. Our findings also suggest that lncRNAs with highly conserved epigenetic and transcriptional regulation across species arose by divergent evolution from a common ancestor, if they do not have identical exon structures.
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影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
影响因子：
4.5
作者：
Korostowski L;Sedlak N;Engel N
通讯作者：
Engel N
影响因子：
10.5
作者：
Mancini-DiNardo, Debora;Steele, Scott J. S.;Tilghman, Shirley M.
通讯作者：
Tilghman, Shirley M.
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.