Measuring the impact of chromatin context on transcription factor binding affinities

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    We have designed a method, binding affinities to native chromatin by sequencing (BANC-seq), to determine the transcription factor concentrations required for binding to regulatory elements across the genome. Our study shows that chromatin context and DNA accessibility are key regulators of transcription factor binding.

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    Fig. 1: Overview of the BANC-seq experimental procedure and interpretation.

    References

    1. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012). An important paper that gives an overview of TF binding across the genome and epigenome.

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    2. Lambert, S. A. et al. The human transcription factors. Cell 172, 650–665 (2018). A review article that provides an in-depth discussion of TF function and regulation.

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    3. Guo, J. et al. Sequence specificity incompletely defines the genome-wide occupancy of Myc. Genome Biol. 15, 482 (2014). A research paper that highlights the importance of features other than DNA sequence for MYC binding.

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    4. Slattery, M. et al. Absence of a simple code: how transcription factors read the genome. Trends Biochem. Sci. 39, 381–399 (2014). A review article that outlines the complex mechanisms that determine TF binding.

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    5. Lindeboom, R. G. et al. Integrative multi-omics analysis of intestinal organoid differentiation. Mol. Syst. Biol. 14, e8227 (2018). An article that reports that substantial increases in TF concentrations lead to binding that cannot be explained with current binding models.

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    Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    This is a summary of: Neikes, H. K. et al. Quantification of absolute transcription factor binding affinities in the native chromatin context using BANC-seq. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01715-w (2023).

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    Cite this article

    Measuring the impact of chromatin context on transcription factor binding affinities.
    Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01752-5

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    • DOI: https://doi.org/10.1038/s41587-023-01752-5

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