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Occupancy maps of 208 chromatin-associated proteins in one human cell type
Nature ( IF 50.5 ) Pub Date : 2020-07-29 , DOI: 10.1038/s41586-020-2023-4
E Christopher Partridge 1 , Surya B Chhetri 1, 2, 3 , Jeremy W Prokop 1, 4 , Ryne C Ramaker 1, 5 , Camden S Jansen 6 , Say-Tar Goh 7 , Mark Mackiewicz 1 , Kimberly M Newberry 1 , Laurel A Brandsmeier 1 , Sarah K Meadows 1 , C Luke Messer 1 , Andrew A Hardigan 1, 5 , Candice J Coppola 2 , Emma C Dean 1, 8 , Shan Jiang 6 , Daniel Savic 9 , Ali Mortazavi 6 , Barbara J Wold 7 , Richard M Myers 1 , Eric M Mendenhall 1, 2
Affiliation  

Transcription factors are DNA-binding proteins that have key roles in gene regulation1,2. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes3–6. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium. ChIP–seq and CETCh–seq data are used to analyse binding maps for 208 transcription factors and other chromatin-associated proteins in a single human cell type, providing a comprehensive catalogue of the transcription factor landscape and gene regulatory networks in these cells.

中文翻译:

一种人类细胞类型中 208 种染色质相关蛋白的占位图

转录因子是 DNA 结合蛋白,在基因调控中起关键作用 1,2。转录调节因子的全基因组占据图对于理解基因调控及其对不同生物过程的影响很重要3-6。然而,人类基因组中编码的 1,600 多个转录因子中只有少数被检测到。在这里,作为 ENCODE(DNA 元素百科全书)项目的一部分,我们展示了来自染色质免疫沉淀的数据和分析,然后使用人类 HepG2 细胞系对 208 种染色质相关蛋白 (CAP) 进行高通量测序 (ChIP-seq) 实验. 这些包括 171 个转录因子和 37 个转录辅因子和染色质调节蛋白,代表了 HepG2 细胞中表达的近四分之一的 CAP。这些 CAP 的结合谱形成主要与启动子或增强子或两者相关的主要组。我们确认并扩展了转录因子的当前 DNA 序列基序目录,并描述了与与主要 ChIP 目标共同富集的其他转录因子对应的基序。例如,FOX 家族基序富含 37 个其他 CAP 的 ChIP-seq 峰。我们表明,主题内容和占用模式可以区分启动子和增强子。该目录揭示了许多 CAP 关联的高占有率目标区域,尽管每个区域仅包含众多相关转录因子中少数的基序。这些分析提供了对定义这种细胞类型的基因调控网络的更完整的概述,并证明 ENCODE 联盟大规模生产工作的有效性。ChIP-seq 和 CETCh-seq 数据用于分析单个人类细胞类型中 208 种转录因子和其他染色质相关蛋白的结合图谱,提供这些细胞中转录因子景观和基因调控网络的综合目录。
更新日期:2020-07-29
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