Abstract

Antigen receptor variable-(diversity)-joining (V(D)J) recombination at the locus encoding the T cell antigen receptor- (Tcrb) is ordered, with D-to-J assembly preceding V-to-DJ joining. The molecular mechanism underlying this 'preferred' order of rearrangement remains unclear. Here we show that the D 23–base pair recombination signal sequence (D 23-RSS) contains a specific AP-1 transcription factor–binding site bound by AP-1 and its component c-Fos expressed at a specific stage. Cell-based recombination assays suggested that c-Fos interacted directly with the RAG recombinase and enhanced its deposition to D 23-RSSs, thus conferring the priority of DJ recombination. Loss of c-Fos decreased Tcrb recombination efficiency and disrupted recombination ordering in vivo. Our results show an unexpected function for c-Fos as a direct regulator of Tcrb recombination, rather than its usual function as a transcription regulator, and provide new insight into the mechanisms of recombination ordering.

1. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
2. Model Animal Research Center, Nanjing University, Nanjing 210093, China.
3. Division of Hematopoiesis Center for AIDS Research, Kumamoto University Kumamoto 860-0811, Japan.

Correspondence to: Xiaolong Liu¹ e-mail: liux@sibs.ac.cn

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