Pharmacological HDAC inhibition impairs pancreatic β-cell function through an epigenome-wide reprogramming

• DOI: 10.1016/j.isci.2023.107231
• Publication Date: 2023-06-30T16:07:00Z
• Authors: Frédérik Oger; Maeva Moreno; Mehdi Derhourhi; Bryan Thiroux; Lionel Berberian; Cyril Bourouh; Emmanuelle Durand; Souhila Amanzouga...; Alaa Badreddine; Etienne Blanc; Olivier Molendi-C...; Laurent Pineau; Gianni Pasquetti; Laure Rolland; Charlène Carney; Florine Bornaque; Emilie Courty; Céline Gheeraert; Jérôme Eeckhoute; David Dombrowicz; Julie Kerr-Conte; François Pattou; Bart Staels; Philippe Froguel; Amélie Bonnefond; Jean-Sébastien An...
• Keywords: Epigenome; Trichostatin A; Chromatin immunoprecipitation; Epigenomics; Reprogramming

Histone deacetylases enzymes (HDACs) are chromatin modifiers that regulate gene expression through deacetylation of lysine residues within specific histone and non-histone proteins. A cell-specific pattern defines the identity insulin-producing pancreatic β cells, yet molecular networks driving this transcriptional specificity not fully understood. Here, we investigated HDAC-dependent mechanisms controlling β-cell function using pan-HDAC inhibitor trichostatin immunoprecipitation assays RNA sequencing experiments. We observed TSA alters insulin secretion associated with transcriptome programming in both mouse human lines, as well on islets. also demonstrated alternative program response to HDAC inhibition is related an epigenome-wide remodeling at promoters enhancers. Our data indicate activity could be required protect against loss unsuitable genes cell fates.