Genome-Wide Measurement and Computational Analysis of Transcription Factor Binding and Chromatin Accessibility in Lymphocytes.
Genome-Wide Measurement and Computational Analysis of Transcription Factor Binding and Chromatin Accessibility in Lymphocytes.
复制标题
淋巴细胞转录因子结合和染色质可及性的全基因组测量和计算分析。
DOI：
10.1002/cpim.84
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发表时间：
2019
影响因子：
--
通讯作者：
Sadiyah MF
中科院分区：
文献类型：
--
作者：
Sadiyah MF
适应性免疫系统的细胞，包括CD 4+和CD 8 +T细胞，以及B细胞，具有经历群体大小、分化状态和功能的动态变化的能力，以抵抗来自外部环境的多样性和时间上随机的威胁。为了实现这一目标，淋巴细胞必须能够以细胞类型特异性方式并响应外部信号快速控制其基因表达程序。这种能力是由转录因子（TF）提供的，它们与不同淋巴细胞亚群中可用的调节DNA元件库结合，以编程细胞类型特异性基因表达。在这里，我们提供了一组利用基于大规模并行测序的方法来绘制全基因组TF结合位点和可接近的染色质的方案，并考虑了其应用于淋巴细胞的独特方面和技术问题。我们展示了如何计算验证和分析对齐的数据，以映射差异富集/可访问的网站，识别富集的DNA序列基序，并检测邻近可访问的DNA元件的核小体的位置。这些技术应用于免疫细胞时，可以增强我们对淋巴细胞内基因表达程序如何控制以协调稳态和疾病中的免疫功能的理解。John Wiley & Sons，Inc._关于我们
Cells of the adaptive immune system, including CD4+and CD8+T cells, as well as B cells, possess the ability to undergo dynamic changes in population size, differentiation state, and function to counteract diverse and temporally stochastic threats from the external environment. To achieve this, lymphocytes must be able to rapidly control their gene‐expression programs in a cell‐type‐specific manner and in response to extrinsic signals. Such capacity is provided by transcription factors (TFs), which bind to the available repertoire of regulatory DNA elements in distinct lymphocyte subsets to program cell‐type‐specific gene expression. Here we provide a set of protocols that utilize massively parallel sequencing–based approaches to map genome‐wide TF‐binding sites and accessible chromatin, with consideration of the unique aspects and technical issues facing their application to lymphocytes. We show how to computationally validate and analyze aligned data to map differentially enriched/accessible sites, identify enriched DNA sequence motifs, and detect the position of nucleosomes adjacent to accessible DNA elements. These techniques, when applied to immune cells, can enhance our understanding of how gene‐expression programs are controlled within lymphocytes to coordinate immune function in homeostasis and disease. © 2019 by John Wiley & Sons, Inc.