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