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Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription

Author

Listed:
  • Liliana Felicia Iannucci

    (University of Pavia
    Veneto Institute of Molecular Medicine)

  • Anna Maria D’Erchia

    (University of Bari “Aldo Moro”)

  • Ernesto Picardi

    (University of Bari “Aldo Moro”)

  • Daniela Bettio

    (University of Padova
    Fondazione Istituto di Ricerca Pediatrica Città della Speranza)

  • Filippo Conca

    (University of Pavia
    Veneto Institute of Molecular Medicine)

  • Nicoletta Concetta Surdo

    (Veneto Institute of Molecular Medicine
    National Research Council of Italy)

  • Giulietta Benedetto

    (Veneto Institute of Molecular Medicine
    National Research Council of Italy)

  • Deborah Musso

    (University of Pavia)

  • Cristina Arrigoni

    (University of Pavia)

  • Marco Lolicato

    (University of Pavia)

  • Mauro Vismara

    (University of Pavia
    Veneto Institute of Molecular Medicine)

  • Francesca Grisan

    (Veneto Institute of Molecular Medicine)

  • Leonardo Salviati

    (University of Padova
    Fondazione Istituto di Ricerca Pediatrica Città della Speranza)

  • Luciano Milanesi

    (National Research Council of Italy)

  • Graziano Pesole

    (University of Bari “Aldo Moro”)

  • Konstantinos Lefkimmiatis

    (University of Pavia
    Veneto Institute of Molecular Medicine
    National Research Council of Italy)

Abstract

The second messenger cyclic AMP regulates many nuclear processes including transcription, pre-mRNA splicing and mitosis. While most functions are attributed to protein kinase A, accumulating evidence suggests that not all nuclear cyclic AMP-dependent effects are mediated by this kinase, implying that other effectors may be involved. Here we explore the nuclear roles of Exchange Protein Activated by cyclic AMP 1. We find that it enters the nucleus where forms reversible biomolecular condensates in response to cyclic AMP. This phenomenon depends on intrinsically disordered regions present at its amino-terminus and is independent of protein kinase A. Finally, we demonstrate that nuclear Exchange Protein Activated by cyclic AMP 1 condensates assemble at genomic loci on chromosome 6 in the proximity of Histone Locus Bodies and promote the transcription of a histone gene cluster. Collectively, our data reveal an unexpected mechanism through which cyclic AMP contributes to nuclear spatial compartmentalization and promotes the transcription of specific genes.

Suggested Citation

  • Liliana Felicia Iannucci & Anna Maria D’Erchia & Ernesto Picardi & Daniela Bettio & Filippo Conca & Nicoletta Concetta Surdo & Giulietta Benedetto & Deborah Musso & Cristina Arrigoni & Marco Lolicato , 2023. "Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41088-x
    DOI: 10.1038/s41467-023-41088-x
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    References listed on IDEAS

    as
    1. Holger Rehmann & Joost Das & Puck Knipscheer & Alfred Wittinghofer & Johannes L. Bos, 2006. "Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state," Nature, Nature, vol. 439(7076), pages 625-628, February.
    2. Johan de Rooij & Fried J. T. Zwartkruis & Mark H. G. Verheijen & Robbert H. Cool & Sebastian M. B. Nijman & Alfred Wittinghofer & Johannes L. Bos, 1998. "Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP," Nature, Nature, vol. 396(6710), pages 474-477, December.
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