Characterization of the zebrafish immunoglobulin heavy chain E(mu)3' enhancer

All examined tetrapod immunoglobulin heavy chain (IgH) loci feature a transcriptional enhancer, Emu, which is located in the J H-Cmu1 intron and required for IgH expression and diversity-generating germline modifications occurring at the locus. Studies of the channel catfish IgH locus however demonstrated only the presence of an enhancer in the Cmu-Cdelta intergenic region, called Emu3'. This enhancer position is predicted to be unfavorable for affinity maturation in fish, and would have been a constraint to the evolution of class switch recombination as it developed in the tetrapods. To determine if Emu3' is a general feature of teleosts, we analyzed the zebrafish IgH locus and found an Emu3'-like enhancer, which shares with catfish Emu3' a core region of homology and a closely spaced pair of E-box motifs. These E-boxes are critical to enhancer function. The presence of similarly spaced E-boxes in the predicted Emu3' regions of other fish species indicate that they may be a common feature of fish IgH enhancers.