Recent progress in understanding transcription factor binding specificity.
Recent progress in understanding transcription factor binding specificity.
复制标题
了解转录因子结合特异性的最新进展。
DOI：
10.1093/bfgp/elu050
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发表时间：
2015
影响因子：
4
通讯作者：
Bussemaker,HarmenJ
中科院分区：
文献类型：
--
作者：
Bussemaker,HarmenJ
基因表达水平在基因与基因之间和个体之间可以有很大差异。为了理解这些差异是如何产生的，并能够预测和操纵它们，我们需要剖析嵌入基因组中的调控程序被细胞机制解释的分子机制。这期《功能基因组学简报》概述了定量反式作用因子核苷酸结合特异性的可用方法，这是理解和预测基因调控网络功能的先决条件。转录因子通常属于包含许多具有相似氨基酸序列的其他蛋白质的结构家族。即使这些蛋白质之间的核苷酸序列偏好差异很小，它们的靶基因以及它们控制的过程也可能非常不同。在一项开创性的微流体研究中，Maerkl和Quake（1）表明，使用定量的、纯粹基于序列的热力学模型来预测这种功能差异是可能的。因此，对基因组中编码的所有转录因子的DNA结合特异性进行全面和准确的定量，可能会改变我们对细胞调控网络进行功能预测的能力。Noyes实验室的第一篇综述（2）描述了细菌单杂交（B1 H）方法，其中蛋白质-DNA相互作用强度通过报告基因的表达来测量。该技术已被用于对同源结构域和锌指家族内DNA结合特异性的变化进行深入分析。B1 H方法的一个独特优势是可以方便地平行测定大量不同的蛋白质序列。
Gene expression levels can vary greatly from gene to gene and between individuals. To understand how these differences arise, and be able to predict and manipulate them, we need to dissect the molecular mechanisms by which the regulatory programs embedded in the genome are interpreted by the cellular machinery. This issue of Briefings in Functional Genomics provides an overview of the available approaches for quantifying the nucleotide binding specificity of trans-acting factors, a prerequisite for understanding and predicting gene regulatory network function.Transcription factors typically belong to a structural family containing many other proteins with a similar amino acid sequence. Even when the difference in nucleotide sequence preference between such proteins is subtle, their target genes, and thus the processes that they control, can be quite distinct. In a pioneering microfluidics study, Maerkl and Quake (1) showed that it is possible to predict such functional differences using a quantitative, purely sequence-based, thermodynamic model. Comprehensive and accurate quantification of the DNA binding specificity of all transcription factors encoded in the genome may therefore transform our ability to make functional predictions about the regulatory network of the cell. A first review by the Noyes laboratory (2) describes the bacterial one-hybrid (B1H) approach, in which protein–DNA interaction strength is measured via expression of a reporter gene. This technology has been used to perform in-depth analyses of the variation in DNA binding specificity within the homeodomain and zinc finger families. A unique advantage of the B1H approach is the ease with which a large number of different protein sequences can be assayed in parallel.
影响因子：
4
作者：
Adam P. Joyce;Chi Zhang;P. Bradley;J. Havranek
通讯作者：
Adam P. Joyce;Chi Zhang;P. Bradley;J. Havranek
影响因子：
4
作者：
Stormo，Gary D.;Zuo，Zheng;Chang，Yiming Kenny
通讯作者：
Chang，Yiming Kenny
影响因子：
4
作者：
Andrilenas, Kellen K.;Penvose, Ashley;Siggers, Trevor
通讯作者：
Siggers, Trevor