摘要
背景:多梳抑制复合物2(PRC 2)催化H3 Lys 27的组蛋白甲基化,在许多系统的发育和疾病过程中起着至关重要的作用。它的催化亚基EZH 2是长非编码RNA(IncRNAs)的关键核靶点,它是一种新兴的表观遗传调节剂,参与多种细胞过程。INcRNA具有较高的组织特异性,但对EZH 2相互作用的IncRNAs的组织特征了解甚少。目的:采用RNA免疫沉淀和RNA测序相结合的方法,对脑、肺、心、肝、肾、肠、脾、睾丸、肌肉和血液等组织中EZH 2结合的INcRNAs进行全局筛选。我们鉴定了1328个EZH_2结合的INcRNAs,其中470个在至少两个组织中共享,858个在单个组织中被检测到。在许多incRNAs中发现了一个具有特殊二级结构的RNA基序,尽管不是所有EZH 2结合的incRNAs。EZH 2结合的INcRNA可分为4类:基因间INcRNA、反义INcRNA、内含子相关INcRNA和启动子相关INcRNA。启动子相关的INcRNA Hnf1aos1与肝脏中的EZH 2特异结合,与其配对编码基因HNF1A具有相同的特征,进一步证实了本研究的有效性。除了已知的EZH 2结合的INcRNAs,如Kcnq1ot1、Gas5、Meg3、Hotair和MALAT 1之外,大多数的INcRNAs被报道与EZH 2有关。结论:我们的发现提供了EZH 2-相互作用于不同组织的INcRNAs的剖面图,并提示了INcRNAs在细胞分化和成熟过程中的关键作用。表观遗传学,长非编码RNA,组织特异性,PRC 2,EZH 2,组蛋白甲基化
关键词: 表观遗传学,长非编码RNA,组织特异性,PRC 2,EZH 2,组蛋白甲基化
Current Gene Therapy
Title:EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs
Volume: 18 Issue: 5
关键词: 表观遗传学,长非编码RNA,组织特异性,PRC 2,EZH 2,组蛋白甲基化
摘要: Background: Polycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator and participate in diverse cellular processes. LncRNAs are characterized by high tissue-specificity; however, little is known about the tissue profile of the EZH2- interacting lncRNAs.
Objective: Here we performed a global screening for EZH2-binding lncRNAs in tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood by combining RNA immuno- precipitation and RNA sequencing. We identified 1328 EZH2-binding lncRNAs, among which 470 were shared in at least two tissues while 858 were only detected in single tissue. An RNA motif with specific secondary structure was identified in a number of lncRNAs, albeit not in all EZH2-binding lncRNAs. The EZH2-binding lncRNAs fell into four categories including intergenic lncRNA, antisense lncRNA, intron-related lncRNA and promoter-related lncRNA, suggesting diverse regulations of both cis and trans-mechanisms. A promoter-related lncRNA Hnf1aos1 bound to EZH2 specifically in the liver, a feature same as its paired coding gene Hnf1a, further confirming the validity of our study. In addition to the well known EZH2-binding lncRNAs like Kcnq1ot1, Gas5, Meg3, Hotair and Malat1, majority of the lncRNAs were firstly reported to be associated with EZH2.
Conclusion: Our findings provide a profiling view of the EZH2-interacting lncRNAs across different tissues, and suggest critical roles of lncRNAs during cell differentiation and maturation.
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EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs, Current Gene Therapy 2018; 18 (5) . https://dx.doi.org/10.2174/1566523218666181008125010
DOI https://dx.doi.org/10.2174/1566523218666181008125010 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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