| First Author | Seo W | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 41351 | PubMed ID | 28150718 |
| Mgi Jnum | J:274549 | Mgi Id | MGI:6296027 |
| Doi | 10.1038/srep41351 | Citation | Seo W, et al. (2017) Distinct requirement of Runx complexes for TCRbeta enhancer activation at distinct developmental stages. Sci Rep 7:41351 |
| abstractText | A TCRbeta enhancer, known as the Ebeta enhancer, plays a critical role in V(D)J recombination and transcription of the Tcrb gene. However, the coordinated action of trans-acting factors in the activation of Ebeta during T cell development remains uncharacterized. Here, we characterized the roles of Runx complexes in the regulation of the Ebeta function. A single mutation at one of the two Runx binding motifs within the Ebeta severely impaired Tcrb activation at the initiation phase in immature thymocytes. However, TCRbeta expression level in mature thymocytes that developed under such a single Runx site mutation was similar to that of the control. In contrast, mutations at two Runx motifs eliminated Ebeta activity, demonstrating that Runx complex binding is essential to initiate Ebeta activation. In cells expressing Tcrb harboring rearranged V(D)J structure, Runx complexes are dispensable to maintain TCRbeta expression, whereas Ebeta itself is continuously required for TCRbeta expression. These findings imply that Runx complexes are essential for Ebeta activation at the initiation phase, but are not necessary for maintaining Ebeta activity at later developmental stages. Collectively, our results indicate that the requirements of trans-acting factor for Ebeta activity are differentially regulated, depending on the developmental stage and cellular activation status. |
