Sidhu, G. A.; Percival-Smith, A.

Transcription factor (TF) function is redundant: TF phenotypes are frequently rescued by TFs not resident to the TF locus, a phenomenon termed phenotypic nonspecificity. Phenotypic nonspecificity in Drosophila melanogaster is not dependent on the DNA binding specificity of the TFs and generally due to genetic complementation. Two TF phenotypes (doublesex [dsx] and apterous [ap]) are rescued by multiple TFs. The rescue by resident TFs, and the rescue and non-rescue by non-resident TFs, of these two phenotypes were used to distinguish between three possible outcomes of the comparison of the TF-dependent mRNA accumulation in these two systems. First, the sets of TF-dependent mRNAs are independent and non-overlapping; second, the sets of TF-dependent mRNAs are independent and overlapping; and third, the sets of TF-dependent mRNAs are constrained and have extensive overlap. The transcriptomes associated with rescue by resident TFs, and rescue and non-rescue by non-resident TFs, of the two TF phenotypes (dsx and ap) provided many examples of extensive overlap indicating regulation of constrained sets of genes. However, the strength of correlation of transcript accumulation observed between the resident and non-resident TFs was not a strong predictor for rescue of the phenotype by the non-resident TFs. The regulation of a constrained set of genes supports the hypothetical assembly of TFs into wolfpacks, and not the hypothetical limited specificity of TF function, as a potential explanation of phenotypic nonspecificity.