Regulation of T cell receptor delta gene rearrangement by c-Myb.

P Lauzurica,C Hernández-Munain,M S Krangel

doi:10.1084/jem.183.1.289

Abstract

Developmental activation of VDJ recombination at the T cell receptor (TCR) delta locus is controlled by an intronic transcriptional enhancer (E delta). Transcriptional activation by E delta is dependent on c-Myb. To determine whether c-Myb plays a role in the activation of TCR-delta gene rearrangement, we compared VDJ recombination in transgenic mice carrying two versions of a human TCR-delta gene minilocus recombination substrate. One includes a wild-type E delta, whereas the other carries an E delta with a mutation that abrogates c-Myb binding. We demonstrate that an intact Myb binding site is necessary for efficient rearrangement of the minilocus substrate, suggesting that c-Myb plays a crucial role in activating VDJ recombination at the endogenous TCR-delta locus.

Highlights

Developmental activation of VDJ recombination at the T cell receptor (TCR) 8 locus is controlled by an intronic transcriptional enhancer (Es)
Gene-targeted c-myb-homozygous mutant mice die in utero and display severe anemia and other defects in hematopoiesis by fetal day 14.5 [3]
Thymocyte genomic DNA templates were analyzed by quantitative PCR, and specific PCR products were identified by hybridization with radiolabeled V81 and Va2 c D N A probes (Fig. 1 B)

Summary

Introduction

Developmental activation of VDJ recombination at the T cell receptor (TCR) 8 locus is controlled by an intronic transcriptional enhancer (Es). Transcriptional activation by E~ is dependent on c-Myb. To determine whether c-Myb plays a role in the activation of TCR-8 gene rearrangement, we compared VDJ recombination in transgenic mice carrying two versions of a human T C R - 8 gene minilocus recombination substrate. One includes a wild-type Es, whereas the other carries an E8 with a mutation that abrogates c-Myb binding. We demonstrate that an intact Myb binding site is necessary for efficient rearrangement of the minilocus substrate, suggesting that c-Myb plays a crucial role in activating VDJ recombination at the endogenous TCR-8 locus

Methods

Results

Discussion

Conclusion