| First Author | Kim D | Year | 2017 |
| Journal | Nucleic Acids Res | Volume | 45 |
| Issue | 9 | Pages | 5112-5125 |
| PubMed ID | 28160598 | Mgi Jnum | J:246285 |
| Mgi Id | MGI:5922941 | Doi | 10.1093/nar/gkx080 |
| Citation | Kim D, et al. (2017) Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation. Nucleic Acids Res 45(9):5112-5125 |
| abstractText | Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance. |
