Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs.
Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs.
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DOI：
10.3389/fgene.2020.590672
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发表时间：
2020
影响因子：
3.7
通讯作者：
Li CQ
中科院分区：
文献类型：
--
作者：
Li XC;Tang ZD;Peng L;Li YY;Qian FC;Zhao JM;Ding LW;Du XJ;Li M;Zhang J;Bai XF;Zhu J;Feng CC;Wang QY;Pan J;Li CQ
环状RNA（circRNA）是进化上保守且丰富的非编码RNA，其功能和调节机制在很大程度上仍未知。在这里，我们确定和表征一组表观基因组不同的circRNA（TAH-circRNA），这是转录到一个更高的水平比他们的宿主基因。通过对cistromic和transcriptomic数据的综合分析，我们发现TAH-circRNA与其他circRNA相比，表达量更丰富，具有更多的转录因子（TF）结合位点和更低的DNA甲基化水平。一致地，TAH-circRNA在开放和活性染色质区域中富集。重要的是，ChIA-PET结果显示TAH-circRNA的23-52%的转录起始位点（TSS）与顺式调控区直接相互作用，强烈表明它们独立于宿主基因的转录调控。此外，我们描述了癌症生物学中超级增强子驱动的circRNA的分子特征。总之，这项研究全面分析了circRNA的表观基因组特征，并确定了一组独特的TAH-circRNA，它们通过TF的增强子和超级增强子独立转录。这些发现大大推进了我们对circRNA调控机制的理解，并可能对这类非编码RNA的未来研究具有重要意义。
Circular RNAs (circRNAs) are evolutionarily conserved and abundant non-coding RNAs whose functions and regulatory mechanisms remain largely unknown. Here, we identify and characterize an epigenomically distinct group of circRNAs (TAH-circRNAs), which are transcribed to a higher level than their host genes. By integrative analysis of cistromic and transcriptomic data, we find that compared with other circRNAs, TAH-circRNAs are expressed more abundantly and have more transcription factors (TFs) binding sites and lower DNA methylation levels. Concordantly, TAH-circRNAs are enriched in open and active chromatin regions. Importantly, ChIA-PET results showed that 23–52% of transcription start sites (TSSs) of TAH-circRNAs have direct interactions with cis-regulatory regions, strongly suggesting their independent transcriptional regulation from host genes. In addition, we characterize molecular features of super-enhancer-driven circRNAs in cancer biology. Together, this study comprehensively analyzes epigenomic characteristics of circRNAs and identifies a distinct group of TAH-circRNAs that are independently transcribed via enhancers and super-enhancers by TFs. These findings substantially advance our understanding of the regulatory mechanism of circRNAs and may have important implications for future investigations of this class of non-coding RNAs.