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Homotypic clusters of transcription factor binding sites: A model system for understanding the physical mechanics of gene expression

Ezer, Daphne and Zabet, Nicolae Radu and Adryan, Boris (2014) 'Homotypic clusters of transcription factor binding sites: A model system for understanding the physical mechanics of gene expression.' Computational and Structural Biotechnology Journal, 10 (17). pp. 63-69. ISSN 2001-0370

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The organization of binding sites in cis-regulatory elements (CREs) can influence gene expression through a combination of physical mechanisms, ranging from direct interactions between TF molecules to DNA looping and transient chromatin interactions. The study of simple and common building blocks in promoters and other CREs allows us to dissect how all of these mechanisms work together. Many adjacent TF binding sites for the same TF species form homotypic clusters, and these CRE architecture building blocks serve as a prime candidate for understanding interacting transcriptional mechanisms. Homotypic clusters are prevalent in both bacterial and eukaryotic genomes, and are present in both promoters as well as more distal enhancer/silencer elements. Here, we review previous theoretical and experimental studies that show how the complexity (number of binding sites) and spatial organization (distance between sites and overall distance from transcription start sites) of homotypic clusters influence gene expression. In particular, we describe how homotypic clusters modulate the temporal dynamics of TF binding, a mechanism that can affect gene expression, but which has not yet been sufficiently characterized. We propose further experiments on homotypic clusters that would be useful in developing mechanistic models of gene expression.

Item Type: Article
Uncontrolled Keywords: Cooperativity; Enhancers; Facilitated diffusion; Massively parallel gene expression assays; Mechanistic models
Subjects: Q Science > QC Physics
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 22 Oct 2015 12:06
Last Modified: 15 Jan 2022 00:34

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