A new mechanism for transcriptional regulation by nuclear hormone receptors during Drosophila development
The Ecdysone receptor (ER, a heterodimer of EcR and Usp, homologs of FXR and RXR, respectively) triggers the onset of key steps during Drosophila metamorphosis in response to fluctuations in the steroid hormone ecdysone. Like RXR, ER is currently thought to activate and repress gene expression depending on the presence of the ligand. However, we found that EcR, Usp and a co-activator HMTase Trithorax-related (TRR) are not involved in gene repression. These proteins are capable of shuttling between the nucleus and cytoplasm in an ecdysone-dependent fashion, and are dependent on each other in binding to all target genes. Surprisingly, at low concentrations of ecdysone, a heme-binding nuclear receptor E75A and a co-repressor SMRTER (homologues of Rev-Erb alpha and SMRT, respectively) are involved in repression of ER-activated genes. One striking example of this is a shift from activation to repression of the key developmental gene BR-C that occurs following the major peak of ecdysone at the transition from larval to pupal stages. These results provide a new, unexpected mechanism of functioning of the Drosophila ER and E75A nuclear receptors, and suggest that this may be a new general mode of gene regulation by nuclear hormone receptors.
Johnston, Danika M, "A new mechanism for transcriptional regulation by nuclear hormone receptors during Drosophila development" (2008). ETD Collection for Thomas Jefferson University. AAI3415775.