LAUSR

The regulation of the initiation of transcription by transcription factors (TFs) is often assumed to be dependent on specific recognition of DNA-binding sites and non-redundant. However, the redundant induction or rescue of a phenotype by TFs, phenotypic non-specificity, challenges this assumption. To assess the frequency of phenotypic non-specificity in the rescue of TF phenotypes, seven TF phenotypes labial (lab), Deformed (Dfd), Sex combs reduced (Scr), Ultrabithorax (Ubx), fruitless (fru), doublesex (dsx) and apterous (ap)) were screened for rescue by the expression of twelve, or more, non-resident TFs. From three hundred and eight assessments of rescue by non-resident TFs, eighteen rescues were identified for six of the seven TF phenotypes. Seventeen of the eighteen rescues were with TFs that recognize distinct DNA binding sites relative to the resident TF. All rescues were non-uniform across pleiotropic TF phenotypes suggesting extensive differential pleiotropy of the rescue. Primarily using RNAi to knockdown expression, and with the exceptions of the requirement of Bric a Brac 1 (BAB1) for female abdominal pigmentation and Myb oncogene like (MYB) for wing development, no evidence was found for a role of the other sixteen non-resident TFs in the TF phenotypes assessed. Therefore, these sixteen rescues are likely due to functional complementation and not due to the expression of an epistatic function in the developmental/behavioral pathway. Phenotypic non-specificity is both differentially pleiotropic and frequent, as on average 1 in 10-20 non-resident TFs rescue a phenotype. These observations will be important in future considerations of TF function.