<strong>β-cell specific</strong> <em><strong>E2f1 </strong></em><strong>deficiency impairs glucose homeostasis, β-cell</strong> <strong>identity and insulin secretion</strong>

• DOI: 10.2337/figshare.22906517
• Publication Date: 2023-05-22T20:26:43Z
• Authors: Frédérik Oger; Cyril Bourouh; Marika Elsa Friano; Emilie Courty; Laure Rolland; Xavier Gromada; Maeva Moreno; Charlène Carney; Nabil Rabhi; Emmanuelle Durand; Souhila Amanzouga...; Lionel Berberian; Mehdi Derhourhi; Etienne Blanc; Sarah Anissa Hannou; Pierre-Damien Den...; Zohra Benfodda; Patrick Meffre; Lluis Fajas; Julie Kerr-Conte; François Pattou; Philippe Froguel; Benoit Pourcet; Amélie Bonnefond; Patrick Collombat; Jean-Sébastien An...
• Keywords: H3K4me3; E2F1; Epigenomics; Chromatin immunoprecipitation; E2F

&lt;p&gt;The loss of pancreatic β-cell identity emerges as an important feature type 2 diabetes development, but the molecular mechanisms are still elusive. Here, we explore cell-autonomous role cell cycle regulator and transcription factor E2F1 in maintenance identity, insulin secretion glucose homeostasis. We show that β-cell-specific &lt;em&gt;E2f1 &lt;/em&gt;function mice triggers intolerance associated with defective secretion, altered endocrine mass, a downregulation many genes concomitant increase non-β-cell markers. Mechanistically, epigenomic profiling promoters these upregulated identified enrichment bivalent H3K4me3/H3K27me3 or H3K27me3 marks. Conversely, downregulated were enriched active chromatin H3K4me3 H3K27ac histone find specific E2f1 transcriptional, cistromic signatures dysfunctions, directly regulating several at level. Finally, pharmacological inhibition E2F transcriptional activity human islets also impairs expression genes. Our data suggest is critical for maintaining function through sustained control non programs. &lt;/p&gt;