Comparative genomics of transcription factors driving expression of the immunoglobulin heavy chain locus in teleost fish

Abstract

The immunoglobulin heavy chain locus of teleost fish is driven by an enhancer (Eμ3′) that contains, in all species examined, octamer and E‐box motifs (typically μE5). Thus, the transcription factors known (through experiments in fish) or predicted (from knowledge of their mammalian homologues) to be involved in the function of the enhancer are the octamer‐binding (Oct) transcription factors Oct1 and Oct2, their coactivator BOB.1 and the μE5‐binding E‐proteins (E2A, HEB and E2‐2). Comparative genomic analysis of the genes encoding these transcription factors in teleost fish permits some conclusions to be drawn concerning the fate of these genes following the genome‐wide duplication event that occurred in this lineage. Although problems in the assembly of some regions of the zebrafish genome may complicate the analysis, the pattern that emerges from these studies is that Oct1, Oct2, BOB.1 and E2‐2 are all single‐copy genes in teleosts, whereas in the case of E2A and HEB, two copies of each gene are present. The evolutionary conservation of sequences between related genes is variable, but with the highest similarities always being observed in the domains with ligand‐binding function, whether the ligand is a DNA motif or, as in the case of BOB.1, another protein domain. A major challenge that must be faced is the assignment of precise functions to these diverse transcription factors in teleosts; assumptions drawn by inference from their mammalian homologues will likely be misleading.

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