Amin Viren, Harris R Alan, Onuchic Vitor, Jackson Andrew R, Charnecki Tim, Paithankar Sameer, Lakshmi Subramanian Sai, Riehle Kevin, Coarfa Cristian, Milosavljevic Aleksandar
Epigenome Center, Bioinformatics Research Laboratory, Department of Molecular &Human, Genetics, Baylor College of Medicine, One Baylor Plaza, BCMD 400D, Houston, Texas 77030, USA.
Nat Commun. 2015 Feb 18;6:6370. doi: 10.1038/ncomms7370.
Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, we determine tissue-specific epigenetic regulation for 3,753 (69% examined) lincRNAs, with 54% active in one of the 14 cell/tissue clusters and an additional 15% in two or three clusters. A larger fraction of lincRNA TSSs is marked in a tissue-specific manner by H3K4me1 than by H3K4me3. The tissue-specific lincRNAs are strongly linked to tissue-specific pathways and undergo distinct chromatin state transitions during cellular differentiation. Polycomb-regulated lincRNAs reside in the bivalent state in embryonic stem cells and many of them undergo H3K27me3-mediated silencing at early stages of differentiation. The exquisitely tissue-specific epigenetic regulation of lincRNAs and the assignment of a majority of them to specific tissue types will inform future studies of this newly discovered class of genes.
长链非编码RNA（lincRNA）的组织特异性表达提示其具有发育和细胞类型特异性功能，但仅一小部分lincRNA的组织特异性得以确立。在此，通过分析美国国立卫生研究院（NIH）表观基因组学路线图计划中的111个参考表观基因组，我们确定了3753个（占检测数量的69%）lincRNA的组织特异性表观遗传调控，其中54%在14个细胞/组织簇中的一个中具有活性，另有15%在两个或三个簇中具有活性。与H3K4me3相比，更大比例的lincRNA转录起始位点（TSS）以组织特异性方式被H3K4me1标记。组织特异性lincRNA与组织特异性途径紧密相连，并在细胞分化过程中经历不同的染色质状态转变。多梳蛋白调控的lincRNA在胚胎干细胞中处于二价状态，其中许多在分化早期经历H3K27me3介导的沉默。lincRNA精细的组织特异性表观遗传调控以及将它们中的大多数归属于特定组织类型，将为未来对这类新发现基因的研究提供信息。
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