The Human and Drosophila ERH are Functionally Equivalent: Evidence from Transgenic Studies

Abstract

The enhancer of rudimentary, e(r), gene encodes a small highly conserved protein, enhancer of rudimentary homolog (ERH), which has been shown to have a regulatory function in cell division, Notch signaling, and cancer progression. Human and Drosophila ERH, both 104 amino acids in length, are 76% identical and 84% similar. The high sequence identity translates into nearly identical tertiary structures. Previous studies on the expression of the human and Drosophila e(r) genes reveal that the two genes are similarly regulated. Data in the present study using an e(r)-eGFP reporter gene confirm these results, showing a high expression of the reporter in the ovaries, testes, and brain. The high structural and regulatory conservation of e(r) and ERH argue that human and Drosophila ERH may be biochemically and functionally equivalent. To test this hypothesis, a chimeric transgene containing the Drosophila e(r) non-coding regions and the human e(r) coding region was constructed and used to establish transgenic Drosophila stocks. This transgene can rescue all of the mutant phenotypes of an e(r) deletion, and Drosophila stocks in which the fly ERH has been replaced with the human ERH are fully healthy and viable. These studies demonstrate that the human and Drosophila ERH are functionally equivalent, suggesting that studies on the activity of the human ERH can be done in Drosophila, where a multitude of genetic and developmental tools are available.