Major {beta} cell-specific functions of NKX2.2 are mediated via the NK2-specific domain [Research Papers]

In this study, we demonstrate that β 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 β cell precursors into mature, insulin-expressing β cells, resulting in overt neonatal diabetes. Within the adult β cell, the SD stimulates β cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for β cell function. These irregularities in β 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.

Source: Genes and Development - July 18, 2023 Category: Genetics & Stem Cells Authors: Abarinov, V., Levine, J. A., Churchill, A. J., Hopwood, B., Deiter, C. S., Guney, M. A., Wells, K. L., Schrunk, J. M., Guo, Y., Hammelman, J., Gifford, D. K., Magnuson, M. A., Wichterle, H., Sussel, L. Tags: Research Papers Source Type: research