title: Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs.
abstract: Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive. Here, we study the importance of the histone variant H3.3 in Caenorhabditis elegans longevity pathways. We show that H3.3-deficient nematodes have negligible lifespan differences compared to wild-type animals. However, H3.3 is essential for the lifespan extension of C. elegans mutants in which pronounced transcriptional changes control longevity programs. Notably, H3.3 loss critically affects the expression of a very large number of genes in long-lived nematodes, resulting in transcriptional profiles similar to wild-type animals. We conclude that H3.3 positively contributes to diverse lifespan-extending signaling pathways, with potential implications on age-related processes in multicellular organisms.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Piazzesi
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Dražen
authors.initials: D
authors.lastname: Papić
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bertan
authors.affiliation: Samantha Dickson Brain Cancer Unit, University College London Cancer Institute (UCL), 72 Huntley Street, London WC1E 6DD, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Salomoni
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Nicotera
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address: daniele.bano@dzne.de.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bano
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D016019:Survival Analysis; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones
keywords: Caenorhabditis elegans; aging; histone variant H3.3; insulin/IGF-1 signaling pathway