| First Author | Abarinov V | Year | 2023 |
| Journal | Genes Dev | Volume | 37 |
| Issue | 11-12 | Pages | 490-504 |
| PubMed ID | 37364986 | Mgi Jnum | J:338878 |
| Mgi Id | MGI:7516038 | Doi | 10.1101/gad.350569.123 |
| Citation | Abarinov V, et al. (2023) Major beta cell-specific functions of NKX2.2 are mediated via the NK2-specific domain. Genes Dev 37(11-12):490-504 |
| abstractText | The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. However, the mechanisms by which TFs establish such precise control over gene expression have remained elusive-especially in instances in which a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that beta cell-specific functions of NKX2.2 are driven by the highly conserved NK2-specific domain (SD). Mutation of the endogenous NKX2.2 SD prevents the developmental progression of beta cell precursors into mature, insulin-expressing beta cells, resulting in overt neonatal diabetes. Within the adult beta cell, the SD stimulates beta cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for beta cell function. These irregularities in beta cell gene expression may be mediated via SD-contingent interactions with components of chromatin remodelers and the nuclear pore complex. However, in stark contrast to these pancreatic phenotypes, the SD is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas versus neuroepithelium. |
