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Publication
Myt Transcription Factors Prevent Stress-Response Gene Overactivation to Enable
Postnatal Pancreatic ß Cell Proliferation, Function, and Survival.
Authors Hu R, Walker E, Huang C, Xu Y, Weng C, Erickson GE, Coldren A, Yang X, Brissova
M, Kaverina I, Balamurugan AN, Wright CVE, Li Y, Stein R, Gu G
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Developmental cell
Year 2020
Date Published 5/1/2020
Volume : Pages 53 : 390 - 405.e10
PubMed Reference 32359405
Abstract 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 ß cells. Thus, we found that co-inactivating the Myt TFs in mouse
pancreatic progenitors compromised postnatal ß 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 ß cells during metabolic stress-induced
compensation but downregulated in dysfunctional type 2 diabetic (T2D) human ß
cells. Lastly, MYT knockdown caused stress-gene overactivation and death in
human EndoC-ßH1 cells. These findings suggest that Myt TFs are essential
restrictors of stress-response overactivity.




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