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How do transcription factors select specific binding sites in the genome?

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How does a transcription factor select a specific DNA response element given the presence of degenerate sequences? To date, this question has largely been viewed from the standpoint of DNA sequence variability and transcription factor binding affinity under steady-state conditions. Here we propose that to address this problem, it is also necessary to account for fluctuating cellular conditions. These lead to dynamic changes in the ensemble of protein (and DNA) conformational states via allosteric effects.

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Figure 1: Schematic illustration of selective binding of transcriptional control proteins to their degenerate response elements under different environmental conditions.
Figure 2: Schematic illustration of the free-energy-landscape shifts associated with the binding of the transcriptional control protein (TC) to various degenerate response elements (RE1, RE2, RE3 and RE4).

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Acknowledgements

This project was funded in whole or in part with federal funds from the US National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Yongping Pan, Chung-Jung Tsai, Buyong Ma and Ruth Nussinov are at the Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, National Cancer Institute–Frederick, Frederick, Maryland, USA.,

    Yongping Pan, Chung-Jung Tsai & Buyong Ma

  2. Department of Human Genetics and Molecular Medicine, Ruth Nussinov is also at the Sackler Institute of Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,

    Ruth Nussinov

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  1. Yongping Pan
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  2. Chung-Jung Tsai
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Correspondence to Ruth Nussinov.

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Pan, Y., Tsai, CJ., Ma, B. et al. How do transcription factors select specific binding sites in the genome?. Nat Struct Mol Biol 16, 1118–1120 (2009). https://doi.org/10.1038/nsmb1109-1118

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