Distinct requirement of Runx complexes for TCR? enhancer activation at distinct developmental stages.

ABSTRACT: A TCR? enhancer, known as the E? 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 E? during T cell development remains uncharacterized. Here, we characterized the roles of Runx complexes in the regulation of the E? function. A single mutation at one of the two Runx binding motifs within the E? severely impaired Tcrb activation at the initiation phase in immature thymocytes. However, TCR? 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 E? activity, demonstrating that Runx complex binding is essential to initiate E? activation. In cells expressing Tcrb harboring rearranged V(D)J structure, Runx complexes are dispensable to maintain TCR? expression, whereas E? itself is continuously required for TCR? expression. These findings imply that Runx complexes are essential for E? activation at the initiation phase, but are not necessary for maintaining E? activity at later developmental stages. Collectively, our results indicate that the requirements of trans-acting factor for E? activity are differentially regulated, depending on the developmental stage and cellular activation status.

SUBMITTER: Seo W 

PROVIDER: S-EPMC5288706 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature