2. Academic Validation
  3. Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells

Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells

  • Biochim Biophys Acta Gene Regul Mech. 2017 Aug;1860(8):870-884. doi: 10.1016/j.bbagrm.2017.06.002.
Maurizio Rossi 1,  Martin Spichty 2,  Lucilla Attorri 3,  Chiara Distante 1,  Clara Nervi 4,  Serafina Salvati 3,  Luigi Vitelli 5
Affiliations

Affiliations

  • 1 Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
  • 2 Laboratory of Biology and Modelling of the Cell, Lyon University, ENS Lyon, University Claude Bernard, CNRS UMR 5239, INSERM U1210, 46 allée d'Italie, Site Jacques Monod, F-69007 Lyon, France.
  • 3 Department of Public Veterinary Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
  • 4 Department of Medical and Surgical Sciences and Biotechnologies, University of Roma "La Sapienza", Corso della Repubblica 79, 04100, Latina, Italy.
  • 5 Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: [email protected].
PMID: 28666847 DOI: 10.1016/j.bbagrm.2017.06.002
Abstract

The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA-cyclic AMP response element-binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]2:ID2:E47 tetrameric complex.In essence, the molecular function of CREB1 is to dynamically regulate the location-specific assembly or disassembly of basic-helix-loop-helix (bHLH):HLH protein complexes to mediate the activation of neural/glial target genes. Together, these findings support the one-to-many binding mechanism of CREB1 and indicate that EPA treatment potentiates the integration of CREB dependent signaling with HLH/bHLH transcriptional network, adding specificity to the CREB1-mediated gene regulation during neural/glial differentiation. Our current research on the EPA-CREB axis could reveal new molecular targets for treating neurogenerative disease.

Keywords

Eicosapentaenoic acid; Embryonic stem cell; HLH protein; Lipid signaling; Multiprotein complex; Transcription factor CREB.

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