| First Author | Hu R | Year | 2020 |
| Journal | Dev Cell | Volume | 53 |
| Issue | 4 | Pages | 390-405.e10 |
| PubMed ID | 32359405 | Mgi Jnum | J:370196 |
| Mgi Id | MGI:8222124 | Doi | 10.1016/j.devcel.2020.04.003 |
| Citation | Hu R, et al. (2020) Myt Transcription Factors Prevent Stress-Response Gene Overactivation to Enable Postnatal Pancreatic beta Cell Proliferation, Function, and Survival. Dev Cell 53(4):390-405.e10 |
| abstractText | Although cellular stress response is important for maintaining function and survival, overactivation of late-stage stress effectors cause dysfunction and death. We show that the myelin transcription factors (TFs) Myt1 (Nzf2), Myt2 (Myt1l, Nztf1, and Png-1), and Myt3 (St18 and Nzf3) prevent such overactivation in islet beta cells. Thus, we found that co-inactivating the Myt TFs in mouse pancreatic progenitors compromised postnatal beta cell function, proliferation, and survival, preceded by upregulation of late-stage stress-response genes activating transcription factors (e.g., Atf4) and heat-shock proteins (Hsps). Myt1 binds putative enhancers of Atf4 and Hsps, whose overexpression largely recapitulated the Myt-mutant phenotypes. Moreover, Myt(MYT)-TF levels were upregulated in mouse and human beta cells during metabolic stress-induced compensation but downregulated in dysfunctional type 2 diabetic (T2D) human beta cells. Lastly, MYT knockdown caused stress-gene overactivation and death in human EndoC-betaH1 cells. These findings suggest that Myt TFs are essential restrictors of stress-response overactivity. |
