Mechanisms of Binding Specificity among bHLH Transcription Factors
1
Neurogenomics Group, Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), DCEXS, Universitat Pompeu Fabra, 08003 Barcelona, Spain
2
Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Margaglione
Int. J. Mol. Sci. 2021, 22(17), 9150; https://doi.org/10.3390/ijms22179150
Received: 27 July 2021
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Revised: 14 August 2021
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Accepted: 18 August 2021
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Published: 24 August 2021
(This article belongs to the Special Issue The Role of Genetic Variation on Transcription Factor Binding Sites in Evolution and Disease)
The transcriptome of every cell is orchestrated by the complex network of interaction between transcription factors (TFs) and their binding sites on DNA. Disruption of this network can result in many forms of organism malfunction but also can be the substrate of positive natural selection. However, understanding the specific determinants of each of these individual TF-DNA interactions is a challenging task as it requires integrating the multiple possible mechanisms by which a given TF ends up interacting with a specific genomic region. These mechanisms include DNA motif preferences, which can be determined by nucleotide sequence but also by DNA’s shape; post-translational modifications of the TF, such as phosphorylation; and dimerization partners and co-factors, which can mediate multiple forms of direct or indirect cooperative binding. Binding can also be affected by epigenetic modifications of putative target regions, including DNA methylation and nucleosome occupancy. In this review, we describe how all these mechanisms have a role and crosstalk in one specific family of TFs, the basic helix-loop-helix (bHLH), with a very conserved DNA binding domain and a similar DNA preferred motif, the E-box. Here, we compile and discuss a rich catalog of strategies used by bHLH to acquire TF-specific genome-wide landscapes of binding sites.
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Keywords:
transcription factor binding sites; E-box; bHLH; co-factors; ChIP-seq; pioneer factors; dimerization
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MDPI and ACS Style
de Martin, X.; Sodaei, R.; Santpere, G. Mechanisms of Binding Specificity among bHLH Transcription Factors. Int. J. Mol. Sci. 2021, 22, 9150. https://doi.org/10.3390/ijms22179150
AMA Style
de Martin X, Sodaei R, Santpere G. Mechanisms of Binding Specificity among bHLH Transcription Factors. International Journal of Molecular Sciences. 2021; 22(17):9150. https://doi.org/10.3390/ijms22179150
Chicago/Turabian Stylede Martin, Xabier, Reza Sodaei, and Gabriel Santpere. 2021. "Mechanisms of Binding Specificity among bHLH Transcription Factors" International Journal of Molecular Sciences 22, no. 17: 9150. https://doi.org/10.3390/ijms22179150
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