Structural and functional constraints are known to play a major role in restricting the path of evolution of protein activities. However, constraints acting on evolving transcriptional regulatory sequences, e.g. enhancers, are largely unknown. Recently, we elucidated how a novel expression pattern of the Neprilysin-1 (Nep1) gene in the optic lobe of Drosophila santomea evolved via co-option of ...

When the gypsy retrotransposon of Drosophila inserts between an enhancer and promoter it prevents the enhancer from activating transcription. Enhancers are blocked because the protein (SUHW) encoded by the suppressor of Hairy-wing [su(Hw)] gene binds to gypsy. For example, gypsy insertions in an 85 kilobase region between a wing margin-specific enhancer and the promoter in the cut gene cause a ...

telencephalon at E9.5–10.5 and cortical ventricular zone later than E12.5. Otx, Tcf, Smad and two sites for unknown transcriptional factors are essential to all these activities. The enhancer is well conserved among tetrapods. The mutant that lacks this enhancer demonstrated that the Emx2 expression under this enhancer is indeed essential to diencephalon, telencephalon and cortical development....

The liganded Ah receptor activates transcription by binding to a specific DNA-recognition motif within a dioxin-responsive enhancer upstream of the CYP1A1 gene. Analyses of mutant enhancers by gel retardation reveal that each base pair within the domain 5'CGTG(GCAC)3' is essential to the receptor-enhancer interaction. The three base pairs immediately flanking each end of the essential domain co...

telencephalon at E9.5–10.5 and cortical ventricular zone later than E12.5. Otx, Tcf, Smad and two sites for unknown transcriptional factors are essential to all these activities. The enhancer is well conserved among tetrapods. The mutant that lacks this enhancer demonstrated that the Emx2 expression under this enhancer is indeed essential to diencephalon, telencephalon and cortical development....

RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here, we characterize mutant RXRA, demonstrating...