FHX.L and FHX.S, two isoforms of the human fork-head factor FHX (FOXJ2) with differential activity

Many biological phenomena are dependent on mechanisms that fine-tune the ex pression levels of particular genes. This can be achieved by altering the r elative activity of a single transcription factor, by post-translational mo difications or by interaction with regulatory molecules. An alternative mec hanism is based on competition between two or more differently active isofo rms of the same transcription factor. We found that FHX, a recently charact erized human fork-head transcriptional activator, may show such a mechanism for balancing its activity by expressing two differently sized isoforms, F HX.S and FHX.L, encoded by a single gene located on human chromosome 12. FH X.L and FHX.S showed different transcriptional capacities, the larger form, FHX.L, behaving as the more potent transactivator. A transactivation domai n of the acidic type present only in FHX.L would account for this functiona l difference. The relative concentrations of these two FHX isoforms appear to vary in a number of cell types, a circumstance that may regulate the fin al activity of this transcription factor. (C) 2000 Academic Press.