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Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription

Iannucci, Liliana Felicia, D’Erchia, Anna Maria, Picardi, Ernesto, Bettio, Daniela, Conca, Filippo, Surdo, Nicoletta Concetta, Di Benedetto, Giulietta, Musso, Deborah, Arrigoni, Cristina, Lolicato, Marco, Vismara, Mauro, Grisan, Francesca, Salviati, Leonardo, Milanesi, Luciano, Pesole, Graziano, Lefkimmiatis, Konstantinos·2023·Nature Communications
DOI 10.1038/s41467-023-41088-xPMC PMC10491619

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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.

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Metadata

Authors
Iannucci, L. F., D’Erchia, A. M., Picardi, E., Bettio, D., Conca, F., Surdo, N. C., Di Benedetto, G., Musso, D., Arrigoni, C., Lolicato, M., Vismara, M., Grisan, F., Salviati, L., Milanesi, L., Pesole, G., & Lefkimmiatis, K.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-09-08
Volume
14
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-023-41088-x
PMC
PMC10491619
Cited by
19
References
1
Language
en
Licence
Funders
  • Human Frontier Science Program (RG0024/2022)
  • Associazione Italiana per la Ricerca sul Cancro (IG2021 ID 26140)
  • -- “Cassa di Risparmio di Padova e Rovigo” (CA.RI.PA.RO) (SIGMI) -- Italian Ministry of University and Scientific Research
  • National Research Program (PNR) Flagship InterOmics Project

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