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Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses

机译:从人内源性逆转录病毒源自治疗元素的系统鉴定与表征

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Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified “HERV/LTR-shared regulatory element (HSRE),” defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG), embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2), hematopoietic TFs (e.g., SPI1 (PU1), GATA1/2, and TAL1), and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/). This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into the transcriptional modulation systems of HERV/LTRs and ancestral HERVs.
机译:人类内源性逆转录病毒(HERVS)和其他长末端重复(LTR) - 型转回转移(HERV / LTR)具有可能影响宿主基因的转录的调节元件。我们系统地识别并基于由编码和路线图表观组织项目提供的97个转录因子(TFS)的可公开的Chip-SEQ数据集进行了这些监管元素。我们使用芯片SEQ数据集确定转录因子结合位点(TFBS)并鉴定在HERV / LTR序列(HERV-TFBS)上观察到的TFBS。总体而言,鉴定了794,972个肝病素材。随后,我们鉴定了“Herv / LTR共享的调节元件(HSRE)”,“在HERV-TFBS中定义为TF结合基序,在肝脏/ LTR类型的大部分内共享。 HSRES可能表明Herv / LTR的调控元素在其插入之前存在。我们确定了2,201个HSRES,包括354 Herv / LTR和84个TF的特定关联。聚类分析表明,Herv / LTR可以根据TF结合模式进行分组; HERV / LTR基团涉及多能TFS(例如,SOX2,POU5F1和纳米),胚胎内胚层/中胚层TFS(例如,GATA4 / 6,SOX17和FOXA1 / 2),造血TFS(例如,SPI1(PU1),GATA1 / 2和TAL1),并确定CTCF。 HERV / LTR的监管要素倾向于在附近定位和/或三维地区与参与免疫应答的基因,表明该调节因素在控制免疫调节网络方面发挥着重要作用。此外,我们在LTR7,LTR5B和LTR5_HS内展示了特异性特异性TF结合,表明在HERV / LTR的基因组侵犯期间发生调节元件的增益或损失。最后,我们构建了Dbherv-Res,赫夫/ LTR监管要素的交互式数据库(http://herv-tfbs.com/)。本研究提供了了解HERV / LTRS对宿主转录的影响,提供了对腰患者的转录调制系统和祖先的患者的洞察力。

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