Transcriptional regulation of the zebrafish activation-induced cytidine deaminase (AID) gene

Activation-induced cytidine deaminase (AID, encoded by Aicda) mediates affinity maturation of immunoglobulin genes. Early studies in mammals indicated that the transcription of Aicda was regulated by a number of transcriptional regulatory regions, including a B-cell specific enhancer in the first intron. However, in our past studies of fish AID genes we found what appeared to be transcriptional suppressive modules in intron 1 and two other conserved (among fishes) non-coding sequences upstream of the zebrafish Aicda. We subsequently found that the zebrafish Aicda upstream and intron 1 ‘suppressive modules’ function cooperatively to activate transcription. Our findings, consistent with recent observations in the mouse, suggest that this regulatory mechanism - achieved through the balance between enhancers and silencers - was acquired early in the evolution of the vertebrate adaptive immune system. Furthermore, these regulatory modules may be useful in the development of reporter transgenes for identifying and tracking Aicda-expressing cells in fish.