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Live-cell p53 single-molecule binding is modulated by C-terminal acetylation and correlates with transcriptional activity

Author

Listed:
  • Alessia Loffreda

    (Centro di Imaging Sperimentale
    European Center for Nanomedicine)

  • Emanuela Jacchetti

    (Centro di Imaging Sperimentale
    Materiali e Ingegneria Chimica “G.Natta”. Politecnico di Milano)

  • Sofia Antunes

    (Centro di Imaging Sperimentale)

  • Paolo Rainone

    (Centro di Imaging Sperimentale
    National Researches Council)

  • Tiziana Daniele

    (Centro di Imaging Sperimentale)

  • Tatsuya Morisaki

    (National Cancer Institute, NIH
    Colorado State University)

  • Marco E. Bianchi

    (Chromatin Dynamics Unit
    Università Vita-Salute San Raffaele)

  • Carlo Tacchetti

    (Centro di Imaging Sperimentale
    Università Vita-Salute San Raffaele)

  • Davide Mazza

    (Centro di Imaging Sperimentale
    European Center for Nanomedicine)

Abstract

Live-cell microscopy has highlighted that transcription factors bind transiently to chromatin but it is not clear if the duration of these binding interactions can be modulated in response to an activation stimulus, and if such modulation can be controlled by post-translational modifications of the transcription factor. We address this question for the tumor suppressor p53 by combining live-cell single-molecule microscopy and single cell in situ measurements of transcription and we show that p53-binding kinetics are modulated following genotoxic stress. The modulation of p53 residence times on chromatin requires C-terminal acetylation—a classical mark for transcriptionally active p53—and correlates with the induction of transcription of target genes such as CDKN1a. We propose a model in which the modification state of the transcription factor determines the coupling between transcription factor abundance and transcriptional activity by tuning the transcription factor residence time on target sites.

Suggested Citation

  • Alessia Loffreda & Emanuela Jacchetti & Sofia Antunes & Paolo Rainone & Tiziana Daniele & Tatsuya Morisaki & Marco E. Bianchi & Carlo Tacchetti & Davide Mazza, 2017. "Live-cell p53 single-molecule binding is modulated by C-terminal acetylation and correlates with transcriptional activity," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00398-7
    DOI: 10.1038/s41467-017-00398-7
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    Cited by:

    1. Matteo Mazzocca & Alessia Loffreda & Emanuele Colombo & Tom Fillot & Daniela Gnani & Paola Falletta & Emanuele Monteleone & Serena Capozi & Edouard Bertrand & Gaelle Legube & Zeno Lavagnino & Carlo Ta, 2023. "Chromatin organization drives the search mechanism of nuclear factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    3. Amir Shahein & Maria López-Malo & Ivan Istomin & Evan J. Olson & Shiyu Cheng & Sebastian J. Maerkl, 2022. "Systematic analysis of low-affinity transcription factor binding site clusters in vitro and in vivo establishes their functional relevance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Pakavarin Louphrasitthiphol & Alessia Loffreda & Vivian Pogenberg & Sarah Picaud & Alexander Schepsky & Hans Friedrichsen & Zhiqiang Zeng & Anahita Lashgari & Benjamin Thomas & E. Elizabeth Patton & M, 2023. "Acetylation reprograms MITF target selectivity and residence time," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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