Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Genome Biology Année : 2018

Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells

Hashem Koohy
  • Fonction : Auteur
Daniel Bolland
  • Fonction : Auteur
Louise Matheson
  • Fonction : Auteur
Claudia Stellato
  • Fonction : Auteur
Andrew Dimond
  • Fonction : Auteur
Csilla Várnai
  • Fonction : Auteur
Peter Chovanec
  • Fonction : Auteur
Raquel Manzano Garcia
  • Fonction : Auteur
Steven Wingett
  • Fonction : Auteur
Paula Freire-Pritchett
  • Fonction : Auteur
Takashi Nagano
  • Fonction : Auteur
Phillip Hawkins
  • Fonction : Auteur
Len Stephens
  • Fonction : Auteur
  • PersonId : 1018769
Sarah Elderkin
  • Fonction : Auteur
Anne Corcoran
  • Fonction : Auteur
Patrick Varga-Weisz
  • Fonction : Auteur

Résumé

Background: Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Results: Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. Conclusions: Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Fichier principal
Vignette du fichier
2018_koohy_Gen_Biol_1.pdf (3.31 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01929162 , version 1 (26-05-2020)

Licence

Paternité

Identifiants

Citer

Hashem Koohy, Daniel Bolland, Louise Matheson, Stefan Schoenfelder, Claudia Stellato, et al.. Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells. Genome Biology, 2018, 19 (1), ⟨10.1186/s13059-018-1489-y⟩. ⟨hal-01929162⟩
221 Consultations
247 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More