1. Structural Biology and Molecular Biophysics
  2. Cell Biology

Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

  1. Ignacio Izeddin
  2. Vincent Récamier
  3. Lana Bosanac
  4. Ibrahim I Cisse
  5. Lydia Boudarene
  6. Claire Dugast-Darzacq
  7. Florence Proux
  8. Olivier Bénichou
  9. Raphaël Voituriez
  10. Olivier Bensaude
  11. Maxime Dahan
  12. Xavier Darzacq  Is a corresponding author
  1. Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, France
  2. Université Pierre et Marie Curie, France
  3. Institut Curie, CNRS UMR168, France
https://doi.org/10.7554/eLife.02230
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  1. Ignacio Izeddin
  2. Vincent Récamier
  3. Lana Bosanac
  4. Ibrahim I Cisse
  5. Lydia Boudarene
  6. Claire Dugast-Darzacq
  7. Florence Proux
  8. Olivier Bénichou
  9. Raphaël Voituriez
  10. Olivier Bensaude
  11. Maxime Dahan
  12. Xavier Darzacq
(2014)
Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus
eLife 3:e02230.
https://doi.org/10.7554/eLife.02230
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  3. Download .RIS

Abstract

Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time.

Article and author information

Author details

  1. Ignacio Izeddin

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  2. Vincent Récamier

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Lana Bosanac

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  4. Ibrahim I Cisse

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  5. Lydia Boudarene

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  6. Claire Dugast-Darzacq

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  7. Florence Proux

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  8. Olivier Bénichou

    Université Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  9. Raphaël Voituriez

    Université Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  10. Olivier Bensaude

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  11. Maxime Dahan

    Institut Curie, CNRS UMR168, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  12. Xavier Darzacq

    Institut de Biologie de l'École normale supérieure (IBENS) CNRS UMR 8197, Paris, France
    For correspondence
    darzacq@ens.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Version history

  1. Received: January 7, 2014
  2. Accepted: June 11, 2014
  3. Accepted Manuscript published: June 12, 2014 (version 1)
  4. Version of Record published: July 15, 2014 (version 2)

Copyright

© 2014, Izeddin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ignacio Izeddin
  2. Vincent Récamier
  3. Lana Bosanac
  4. Ibrahim I Cisse
  5. Lydia Boudarene
  6. Claire Dugast-Darzacq
  7. Florence Proux
  8. Olivier Bénichou
  9. Raphaël Voituriez
  10. Olivier Bensaude
  11. Maxime Dahan
  12. Xavier Darzacq
(2014)
Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus
eLife 3:e02230.
https://doi.org/10.7554/eLife.02230

Share this article

https://doi.org/10.7554/eLife.02230

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