Titre :

The HDAC inhibitor trichostatin A impairs pancreatic b-cell function through an epigenome-wide reprogramming

Auteur(s) :

Oger, Frédérik [Auteur]
Moreno, Maeva [Auteur]
Derhourhi, Mehdi [Auteur]
Thiroux, Bryan [Auteur]
Berberian, Lionel [Auteur]
Bourouh, Cyril [Auteur]
Durand, Emmanuelle [Auteur]
Amanzougarene, Souhila [Auteur]
Badreddine, Alaa [Auteur]
Blanc, Etienne [Auteur]
Molendi-Coste, Olivier [Auteur]
Pineau, Laurent [Auteur]
Pasquetti, Gianni [Auteur]
Rolland, Laure [Auteur]
Carney, Charlène [Auteur]
Bornaque, Florine [Auteur]
Courty, Emilie [Auteur]
Gheeraert, Céline [Auteur]
Eeckhoute, Jérôme [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Université de Lille
Institut Pasteur de Lille
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Dombrowicz, David [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Kerr-Conte, Julie [Auteur]
Pattou, François [Auteur]
Staels, Bart [Auteur]
Froguel, Philippe [Auteur]
Bonnefond, Amelie [Auteur]
Annicotte, Jean-Sébastien [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]

Date de publication :

2022-12-15

Mot(s)-clé(s) en anglais :

epigenome HDAC insulin secretion pancreatic beta cell
epigenome
HDAC
insulin secretion
pancreatic beta cell

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Objective: The pancreatic islets of Langerhans contain distinct cell subtypes including insulin-producing b cells. Although their cell-specific gene expression pattern defines their identity, the underlying molecular network ...
Lire la suite >Objective: The pancreatic islets of Langerhans contain distinct cell subtypes including insulin-producing b cells. Although their cell-specific gene expression pattern defines their identity, the underlying molecular network driving this transcriptional specificity is not fully understood. Among the numerous transcriptional regulators, histone deacetylases (HDAC) enzymes are potent chromatin modifiers which directly regulate gene expression through deacetylation of lysine residues within specific histone proteins. The precise molecular mechanisms underlying HDAC effects on cellular plasticity and b-cell identity are currently unknown. Methods: The pharmacological inhibition of HDAC activity by trichostatin A (TSA) was studied in the mouse Min6 and human EndocBH1 cell lines, as well as primary mouse sorted b cells and human pancreatic islets. The molecular and functional effects of treating these complementary β-cell models with TSA was explored at the epigenomic and transcriptomic level through next-generation sequencing of chromatin immunoprecipitation (ChIP) assays (ChIP-seq) and RNA sequencing (RNA-seq) experiments, respectively. Results: We showed that TSA alters insulin secretion associated with b-cell specific transcriptome programming in both mouse and human b-cell lines, as well as on human pancreatic islets. We also demonstrated that this alternative b-cell transcriptional program in response to HDAC inhibition is related to an epigenomewide remodeling at both promoters and enhancers. Conclusions: Taken together, our data indicate that full HDAC activity is required to safeguard the epigenome, to protect against loss of β-cell identity with unsuitable expression of genes associated with alternative cell fates.Lire moins >

Langue :

Anglais

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL