J. Biol. Chem., 2020 · DOI: 10.1074/jbc.RA119.011163 · Published: January 13, 2020
The protein NKX2-2 is important for cell development in many tissues. In the central nervous system, it helps in the formation of oligodendrocytes (OLs), which are cells that produce myelin. This study looks at which parts of the NKX2-2 protein are responsible for its function in OL cells. The study found that two regions of NKX2-2, the N-terminal Tinman domain and the C-terminal domain, work together to promote OL differentiation. They do this by attracting other proteins called transcriptional corepressors, like GRG3, HDAC1, and DNMT3A. Another region, the NK2-specific domain, seems to reduce the activity of the C-terminal domain. Overall, NKX2-2 controls OL differentiation by using multiple cofactors and mechanisms to turn off certain genes.
Provides insights into the molecular mechanisms controlling oligodendrocyte differentiation, which is crucial for understanding myelination in the central nervous system.
The identification of specific domains and cofactors involved in NKX2-2 function could lead to the development of targeted therapies for demyelinating diseases such as multiple sclerosis.
The study highlights the complex regulation of gene expression by transcription factors and corepressors, offering a model for understanding similar processes in other developmental contexts.