| First Author | Elhanani O | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 5 | Pages | 107591 |
| PubMed ID | 32375045 | Mgi Jnum | J:314407 |
| Mgi Id | MGI:6715287 | Doi | 10.1016/j.celrep.2020.107591 |
| Citation | Elhanani O, et al. (2020) REST Inhibits Direct Reprogramming of Pancreatic Exocrine to Endocrine Cells by Preventing PDX1-Mediated Activation of Endocrine Genes. Cell Rep 31(5):107591 |
| abstractText | The emerging appreciation of plasticity among pancreatic lineages has created interest in harnessing cellular reprogramming for beta cell replacement therapy of diabetes. Current reprogramming methodologies are inefficient, largely because of a limited understanding of the underlying mechanisms. Using an in vitro reprogramming system, we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for beta cell gene expression in the reprogramming of pancreatic exocrine cells. We observe that REST-bound loci lie adjacent to the binding sites of multiple key beta cell transcription factors, including PDX1. Accordingly, a loss of REST function combined with PDX1 expression results in the synergistic activation of endocrine genes. This is accompanied by increased histone acetylation and PDX1 binding at endocrine gene loci. Collectively, our data identify a mechanism for REST activity involving the prevention of PDX1-mediated activation of endocrine genes and uncover REST downregulation and the resulting chromatin alterations as key events in beta cell reprogramming. |
