A male-specific effect of dominant-negative Fos.

The transcription factor Fos contains a basic DNA binding domain combined with a leucine zipper (bZip). Expression of a truncated form of Fos in Drosophila that contains only the bZip region (Fos bZip) elicits phenotypes resembling fos mutations. These effects presumably derive from competition between wild-type and truncated forms for dimerization partners, with the truncation acting in a dominant-negative manner. We found that expression of Fos bZip elicits male-specific phenotypes. Moreover, genetic interactions occur between Fos bZip and mutations in loci encoding the X chromosome dosage compensation complex. Fos bZip effects are correlated with aberrant male X chromosome structure and depressed signaling through the X-linked Notch locus. Unexpectedly, the male-specific effects are not reproduced with Fos RNAi, suggesting that Fos bZip can be neomorphic in nature. These results provide insight into how mutations in bZip proteins can exhibit gain of function activity. Developmental Dynamics 237:3361–3372, 2008. © 2008 Wiley-Liss, Inc.