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长链非编码RNA uc.4通过改变DNA甲基化来抑制心脏发育中的细胞分化。

Long noncoding RNA uc.4 inhibits cell differentiation in heart development by altering DNA methylation.

作者信息

Zhang Qijun, Feng Mengwen, Zhang Hao, Xu Jia, Zhang Li, Wang Xuejun, Cheng Zijie, Qian Lingmei

机构信息

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

J Cell Biochem. 2019 May;120(5):8061-8068. doi: 10.1002/jcb.28084. Epub 2018 Nov 13.

Abstract

In previous studies, we have demonstrated that long noncoding RNA uc.4 may influence the cell differentiation through the TGF-β signaling pathway, suppressed the heart development of zebrafish and resulting cardiac malformation. DNA methylation plays a significant role in the heart development and disordered of DNA methylation may cause disruption of control of gene promoter. In this study, methylated DNA immunoprecipitation was performed to identify the different expression levels of methylation regions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to identify the possible biological process and pathway that uc.4 may join, associated with Rap1 signaling pathway, gonadotropin-releasing hormone signaling pathway, and Calcium signaling pathway. We found that the distribution of differentially methylated regions peaks was mainly located in intergenic and intron regions. Altogether, our result showed that differentially methylated genes are significantly expressed in uc.4-overexpression cells, providing valuable data for further exploration of the role of uc.4 in heart development.

摘要

在先前的研究中,我们已经证明长链非编码RNA uc.4可能通过TGF-β信号通路影响细胞分化,抑制斑马鱼的心脏发育并导致心脏畸形。DNA甲基化在心脏发育中起重要作用,DNA甲基化紊乱可能导致基因启动子控制的破坏。在本研究中,进行了甲基化DNA免疫沉淀以鉴定甲基化区域的不同表达水平。还进行了基因本体论和京都基因与基因组百科全书(KEGG)分析,以鉴定uc.4可能参与的潜在生物学过程和途径,这些过程和途径与Rap1信号通路、促性腺激素释放激素信号通路和钙信号通路有关。我们发现差异甲基化区域峰的分布主要位于基因间和内含子区域。总之,我们的结果表明差异甲基化基因在uc.4过表达细胞中显著表达,为进一步探索uc.4在心脏发育中的作用提供了有价值的数据。

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