Deciphering the complexity of human non-coding promoter-proximal transcriptome
Deciphering the complexity of human non-coding promoter-proximal transcriptome
复制标题
破译人类非编码启动子近端转录组的复杂性
DOI：
10.1093/bioinformatics/bty981
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发表时间：
2019
期刊：
影响因子：
5.8
通讯作者：
Mapelli S
中科院分区：
文献类型：
--
作者：
Mapelli S
动机长非编码 RNA (lncRNA) 在表观遗传调控和核功能组织中的重要性日益增强。高通量测序方法揭示了启动子近端区域频繁的非编码转录。然而，缺少启动子相关 RNA (paRNA) 的全面目录以及对与邻近基因和基因组调控元件可能相互作用的分析。结果整合来自多种细胞类型和实验平台的数据，我们在人类基因组中鉴定了数千个 paRNA。 paRNA 以有义和反义方向转录，大部分是非聚腺苷酸化的并保留在细胞核中。 paRNA 阳性启动子富含转录调节因子、表观遗传效应因子和激活染色质标记。此外，paRNA 阳性启动子表现出活性启动子和增强子的染色质特征。具有 paRNA 的启动子优先位于染色质环边界，表明参与锚定位点识别和染色质环。重要的是，这些特征独立于邻近基因的转录状态。因此，paRNA 可能充当 ascis 调节模块，对转录因子的局部募集、表观遗传状态和染色质环组织产生影响。这项研究对启动子近端转录组进行了全面分析，并为 paRNA 在表观遗传过程和人类疾病中的作用提供了新的见解。 可用性和实施预测 paRNA 的基因组坐标可在 https://figshare.com 上获得：https://doi.org/10.6084/m9.figshare.7392791.v1 和https://doi.org/10.6084/m9.figshare.4856630.v2.补充信息补充数据可在生物信息学在线获取。
MotivationLong non-coding RNAs (lncRNAs) have gained increasing relevance in epigenetic regulation and nuclear functional organization. High-throughput sequencing approaches have revealed frequent non-coding transcription in promoter-proximal regions. However, a comprehensive catalogue of promoter-associated RNAs (paRNAs) and an analysis of the possible interactions with neighboring genes and genomic regulatory elements are missing.ResultsIntegrating data from multiple cell types and experimental platforms we identified thousands of paRNAs in the human genome. paRNAs are transcribed in both sense and antisense orientation, are mostly non-polyadenylated and retained in the cell nucleus. Transcriptional regulators, epigenetic effectors and activating chromatin marks are enriched in paRNA-positive promoters. Furthermore, paRNA-positive promoters exhibit chromatin signatures of both active promoters and enhancers. Promoters with paRNAs reside preferentially at chromatin loop boundaries, suggesting an involvement in anchor site recognition and chromatin looping. Importantly, these features are independent of the transcriptional state of neighboring genes. Thus, paRNAs may act ascis-regulatory modules with an impact on local recruitment of transcription factors, epigenetic state and chromatin loop organization. This study provides a comprehensive analysis of the promoter-proximal transcriptome and offers novel insights into the roles of paRNAs in epigenetic processes and human diseases.Availability and implementationGenomic coordinates of predicted paRNAs are available at https://figshare.com: https://doi.org/10.6084/m9.figshare.7392791.v1 and https://doi.org/10.6084/m9.figshare.4856630.v2.Supplementary informationSupplementary data are available atBioinformaticsonline.
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影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
16.6
作者：
Pisignano G;Napoli S;Magistri M;Mapelli SN;Pastori C;Di Marco S;Civenni G;Albino D;Enriquez C;Allegrini S;Mitra A;D'Ambrosio G;Mello-Grand M;Chiorino G;Garcia-Escudero R;Varani G;Carbone GM;Catapano CV
通讯作者：
Catapano CV
影响因子：
64.5
作者：
Rao SS;Huntley MH;Durand NC;Stamenova EK;Bochkov ID;Robinson JT;Sanborn AL;Machol I;Omer AD;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
4.4
作者：
Lepoivre C;Belhocine M;Bergon A;Griffon A;Yammine M;Vanhille L;Zacarias-Cabeza J;Garibal MA;Koch F;Maqbool MA;Fenouil R;Loriod B;Holota H;Gut M;Gut I;Imbert J;Andrau JC;Puthier D;Spicuglia S
通讯作者：
Spicuglia S