|Start Date / Time||April 10, 2019 at 9:00 AM|
|End Date / Time||April 10, 2019 at 10:00 AM|
|Location||9455 MRB IV|
|Presenter Name||Xiao-Dun Yang|
|Presentation Title||“The roles of Sin3A co-regulator in endocrine progenitor and differentiated islet cells”|
|Status||This meeting has already occurred|
The previous data from the Gu lab showed that Myt factors (myelin transcription factors) regulated islet-cell differentiation and tuned beta-cell stress responses. However, it is not clear what co-regulators may be recruited by Myt factors to regulate the expression of cell fate genes or stress genes in beta cells. Sin3A (SWI-independent-3A) is a transcriptional co-regulator that interacts with transcription factors (TFs) to recruit chromatin-modifying enzymes to regulate target gene transcription. Sin3A has been shown to associate with Myt factors in large protein complexes in pancreatic beta cells. The interaction between Sin3A and Myt factors is also supported by the evidence that in neuronal cells, the Sin3A close paralog, Sin3B, directly interacts with Myt factors to repress target gene expression. This study focuses on how Sin3A regulates beta-cell differentiation, function, and survival at least partly by interacting with Myt factors. I have inactivated Sin3A in the pancreatic endocrine progenitors and pancreatic progenitors using Ngn3-Cre and Pdx1-Cre, respectively. I will present the phenotypes of the Sin3A-knockout mice and the cellular and molecular mechanisms of these phenotypes. My data indicate that Sin3A is not required for beta-cell differentiation during embryogenesis but is required for postnatal beta-cell function and survival at least partly by tuning the stress responses. This study may indicate a novel mechanism of how beta cells regulate the stress responses within proper levels to maintain normal function and survival, which might provide new clues to treat cellular stress-induced loss of functional beta-cell mass in diabetes.