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Brief Definitive Report |
Chain Intronic Enhancer in Activating V J Rearrangement
Address correspondence to Yang Xu, Div. of Biological Sciences, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0322. Phone: (858) 822-1084; Fax: (858) 534-0053; email: yangxu{at}ucsd.edu
The immunoglobulin
light chain intronic enhancer (iE) activates rearrangement and is required to maintain the earlier or more efficient rearrangement of versus lambda (
). To understand the mechanism of how iE regulates rearrangement, we employed homologous recombination to mutate individual functional motifs within iE in the endogenous locus, including the NF-B binding site (B), as well as E1, E2, and E3 E boxes. Analysis of the impacts of these mutations revealed that E2 and to a lesser extent E1, but not E3, were important for activating rearrangement. Surprisingly, mutation of the B site had no apparent effect on rearrangement. Comparable to the deletion of the entire iE, simultaneous mutation of E1 and E2 reduces the efficiency of rearrangement much more dramatically than either E1 or E2 mutation alone. Because E2A family proteins are the only known factors that bind to these E boxes, these findings provide unambiguous evidence that E2A is a key regulator of rearrangement.
Key Words: B cell development • V(D)J recombination • accessibility • monospecificity • transcription factor
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