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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
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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.
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Overall design |
Transcriptomic profiling of TSA-treated Min6 cells, mouse beta cell sorted, EndoCbH1 cells and human islets of Langerhans
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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 |
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Submission date |
Jun 05, 2023 |
Last update date |
Aug 09, 2023 |
Contact name |
Frederik Oger |
E-mail(s) |
frederik.oger@univ-lille.fr
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Organization name |
Université de Lille
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Lab |
Inserm 1283/CNRS 8199
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Street address |
Faculté de Médecine - Pôle Recherche - 2eme etage - 1 place de Verdun
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City |
Lille |
ZIP/Postal code |
59045 |
Country |
France |
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Platforms (3) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (24)
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Relations |
BioProject |
PRJNA980205 |
Supplementary file |
Size |
Download |
File type/resource |
GSE234148_RAW.tar |
32.8 Mb |
(http)(custom) |
TAR (of RESULTS) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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