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The CRTC-1 transcriptional domain is required for COMPASS complex-mediated longevity in C. elegans.
Silva-García, Carlos G; Láscarez-Lagunas, Laura I; Papsdorf, Katharina; Heintz, Caroline; Prabhakar, Aditi; Morrow, Christopher S; Pajuelo Torres, Lourdes; Sharma, Arpit; Liu, Jihe; Colaiácovo, Monica P; Brunet, Anne; Mair, William B.
Afiliación
  • Silva-García CG; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Láscarez-Lagunas LI; Center on the Biology of Aging, Brown University, Providence, RI, USA.
  • Papsdorf K; Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
  • Heintz C; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Prabhakar A; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Morrow CS; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Pajuelo Torres L; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Sharma A; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Liu J; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Colaiácovo MP; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Brunet A; Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Mair WB; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nat Aging ; 3(11): 1358-1371, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37946042
ABSTRACT
Loss of function during aging is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caenorhabditis elegans / Longevidad Límite: Animals Idioma: En Revista: Nat Aging Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caenorhabditis elegans / Longevidad Límite: Animals Idioma: En Revista: Nat Aging Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos