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Series GSE234148 Query DataSets for GSE234148
Status Public on Aug 08, 2023
Title Pharmacological HDAC inhibition impairs pancreatic β-cell function through a genome-wide epigenomic reprogramming [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Histone deacetylases (HDAC) enzymes are chromatin modifiers which directly regulate gene expression through deacetylation of lysine residues within specific histone and non-histone proteins. A cell-specific gene expression pattern defines the identity of insulin-producing pancreatic b cells, yet molecular networks driving this transcriptional specificity are not fully understood. Here, we investigated the HDAC-dependent molecular mechanisms controlling pancreatic b-cell identity and function using trichostatin A (TSA), a pan-HDAC inhibitor. We observed 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 epigenome-wide remodeling at both promoters and enhancers. 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.
Overall design Transcriptomic profiling of TSA-treated Min6 cells, mouse beta cell sorted, EndoCbH1 cells and human islets of Langerhans
Contributor(s) Oger F, Moreno M, Derhourhi M, Thiroux B, Berberian L, Bourouh C, Durand E, Amanzougarene S, Badreddine A, Blanc E, Molendi-Coste O, Pineau L, Pasquetti G, Rolland L, Carney C, Bornaque F, Courty E, Gheeraert C, Eeckhoute J, Dombrowicz D, Kerr-Conte J, Pattou F, Staels B, Froguel P, Bonnefond A, Annicotte J
Citation(s) 37496675
Submission date Jun 05, 2023
Last update date Aug 09, 2023
Contact name Frederik Oger
Organization name Université de Lille
Lab Inserm 1283/CNRS 8199
Street address Faculté de Médecine - Pôle Recherche - 2eme etage - 1 place de Verdun
City Lille
ZIP/Postal code 59045
Country France
Platforms (3)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (24)
GSM7448560 DMSO treated EndoCβH1 cells_rep_1
GSM7448561 DMSO treated EndoCβH1 cells_rep_2
GSM7448562 DMSO treated EndoCβH1 cells_rep_3
BioProject PRJNA980205

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Supplementary file Size Download File type/resource
GSE234148_RAW.tar 32.8 Mb (http)(custom) TAR (of RESULTS)
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Raw data are available in SRA
Processed data provided as supplementary file

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