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科学家绘制出单个人类细胞类型中208个染色质相关蛋白的占据图谱

励志人生网 2020-08-02 00:02 励志人物 91次

本期文章:《自然》:Online/在线发表

美国阿拉巴马大学Eric M. Mendenhall、Richard M. Myers等研究人员,合作绘制出单个人类细胞类型中208个染色质相关蛋白的占据图谱。相关论文于2020年7月29日发表在《自然》杂志上。

作为ENCODE(Encyclopedia of DNA Elements)项目的一部分,研究人员介绍了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个染色质相关蛋白(CAP)进行了高通量测序(ChIP-seq)实验。它们包含171个转录因子和37个转录辅因子以及染色质调节蛋白,占HepG2细胞中CAP的近四分之一。这些CAP的结合形成主要与启动子或增强子或两者相关的主要类别。

 

研究人员确认并扩大了转录因子的DNA序列基序目录,并描述了与其他转录因子相对应的基序。例如,FOX家族的基序丰富了其他37个CAP的ChIP-seq峰。研究人员发现,基序内容和占用模式可以区分启动子和增强子。这些结果揭示了许多CAP关联的高占据靶标区域,尽管每个CAP仅包含众多关联转录因子中的少数转录因子基序。这些分析为定义这种细胞类型的基因调控网络提供了更完整的概述,并证明了ENCODE联盟大规模工作的有用性。

 

据了解,转录因子是DNA结合蛋白,在基因调节中具有关键作用。转录调节子的全基因组占据图谱对于理解基因调节及其对多种生物过程的影响非常重要。但是,目前仅分析了人类基因组中1600多种转录因子中的少数。

 

附:英文原文

Title: Occupancy maps of 208 chromatin-associated proteins in one human cell type

Author: E. Christopher Partridge, Surya B. Chhetri, Jeremy W. Prokop, Ryne C. Ramaker, Camden S. Jansen, Say-Tar Goh, Mark Mackiewicz, Kimberly M. Newberry, Laurel A. Brandsmeier, Sarah K. Meadows, C. Luke Messer, Andrew A. Hardigan, Candice J. Coppola, Emma C. Dean, Shan Jiang, Daniel Savic, Ali Mortazavi, Barbara J. Wold, Richard M. Myers, Eric M. Mendenhall

Issue&Volume: 2020-07-29

Abstract: 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 processes3,4,5,6. 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.

DOI: 10.1038/s41586-020-2023-4

Source: https://www.nature.com/articles/s41586-020-2023-4

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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