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Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes.
Annual Review of Cell and Developmental Biology ( IF 11.3 ) Pub Date : 2019-07-05 , DOI: 10.1146/annurev-cellbio-100617-062719
Judith F Kribelbauer 1, 2 , Chaitanya Rastogi 1, 2 , Harmen J Bussemaker 1, 2 , Richard S Mann 2, 3, 4
Affiliation  

Eukaryotic transcription factors (TFs) from the same structural family tend to bind similar DNA sequences, despite the ability of these TFs to execute distinct functions in vivo. The cell partly resolves this specificity paradox through combinatorial strategies and the use of low-affinity binding sites, which are better able to distinguish between similar TFs. However, because these sites have low affinity, it is challenging to understand how TFs recognize them in vivo. Here, we summarize recent findings and technological advancements that allow for the quantification and mechanistic interpretation of TF recognition across a wide range of affinities. We propose a model that integrates insights from the fields of genetics and cell biology to provide further conceptual understanding of TF binding specificity. We argue that in eukaryotes, target specificity is driven by an inhomogeneous 3D nuclear distribution of TFs and by variation in DNA binding affinity such that locally elevated TF concentration allows low-affinity binding sites to be functional.

中文翻译:

真核生物中的低亲和力结合位点和转录因子特异性悖论。

尽管这些TFs具有在体内执行不同功能的能力,但来自相同结构家族的真核转录因子(TFs)往往会结合相似的DNA序列。细胞通过组合策略和低亲和力结合位点的使用,部分解决了这种特异性悖论,这能够更好地区分相似的TF。但是,由于这些位点的亲和力低,要理解TF在体内如何识别它们具有挑战性。在这里,我们总结了最近的发现和技术进步,这些发现和技术进步使得可以在广泛的相似性范围内对TF识别进行量化和机械解释。我们提出了一个模型,该模型整合了遗传学和细胞生物学领域的见解,以提供对TF结合特异性的进一步概念性理解。我们认为在真核生物中
更新日期:2020-04-21
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