Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes
| Autor: | Richard S. Mann, Judith F. Kribelbauer, Chaitanya Rastogi, Harmen J. Bussemaker |
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| Rok vydání: | 2019 |
| Předmět: |
Cell
Computational biology Regulatory Sequences Nucleic Acid Biology Article DNA sequencing 03 medical and health sciences 0302 clinical medicine Low affinity medicine Transcriptional regulation Animals Humans natural sciences Binding site Transcription factor 030304 developmental biology 0303 health sciences Binding Sites Eukaryotic transcription Eukaryota Cell Biology Affinities medicine.anatomical_structure Gene Expression Regulation 030217 neurology & neurosurgery Transcription Factors Developmental Biology |
| Zdroj: | Annual Review of Cell and Developmental Biology. 35:357-379 |
| ISSN: | 1530-8995 1081-0706 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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