Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.
Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.
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DOI：
10.1189/jlb.6ta1014-477rr
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发表时间：
2015-05
影响因子：
5.5
通讯作者：
Hume DA
中科院分区：
文献类型：
--
作者：
Joshi A;Pooley C;Freeman TC;Lennartsson A;Babina M;Schmidl C;Geijtenbeek T;FANTOM Consortium;Michoel T;Severin J;Itoh M;Lassmann T;Kawaji H;Hayashizaki Y;Carninci P;Forrest AR;Rehli M;Hume DA
通过整合来自骨髓谱系和AML细胞系的91个样本来分析骨髓转录组，以预测新的调控相互作用、增强子、miRNA和lincRNA。骨髓细胞从其祖细胞的产生在转录水平上通过影响细胞命运选择的关键转录因子的组合控制来调节。为了揭示这一过程在转录水平上的全局动态，我们通过使用CAGE分析生成了91种人类骨髓来源细胞类型的转录谱。这些样本的CAGE测序使我们能够研究骨髓细胞生成过程中转录控制的各个方面，例如鉴定新的转录因子、miRNA和髓系特异性非编码RNA。我们进一步重建了一个转录调控网络聚类共表达的转录本，并将它们与丰富的顺式调控基序。通过使用双向表达作为增强子的替代，我们预测了超过2000个新的增强子，包括IRF8下游38 kb的增强子和KIT基因座中的内含子增强子。最后，我们强调了这些数据的相关性，以解剖粒细胞前体细胞逐步成熟过程中的转录动力学。可获得骨髓转录组的多方面分析（www.myeloidome.roslin.ed.ac.uk）。这个高质量的数据集提供了一个强大的资源来研究骨髓生成过程中的转录调控，并推断人类先天免疫中未注释基因的可能功能。
Analysis of the myeloid transcriptome by integrating 91 samples from the myeloid lineage and AML cell lines to predict novel regulatory interactions, enhancers, miRNAs, and lincRNAs. The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity.