Abstract
Differentially methylated regions have been characterized at a number of imprinted gene complexes with important roles in the regulation of monoallelic expression of one or more genes. The differentially methylated imprinting control region (ICR) located upstream of the murine H19 gene has been shown to control the imprinted expression of H19 and the coordinately regulated Igf2 gene by acting as a transcriptional silencer. In this study, we show that the murine ICR maintains this function when tested in an in vivo transgenic Drosophila assay in the absence of DNA methylation. Furthermore, the H19 ICR interacts distinctively with Drosophila promoters of different regulatory strengths. We also demonstrate that the comparable region upstream of the human H19 gene is a multipartite cis-regulatory element, demonstrating silencing function when tested in mammalian and Drosophila systems. These results indicate a conservation of the H19/Igf2 imprinting mechanism between humans and mice and further elucidate the functional activities of the H19 ICR. They demonstrate the value of Drosophila as an in vivo system for testing function and interaction of eukaryotic regulatory elements and that mechanisms of transcriptional cis-regulation in mammals and Drosophila are conserved.
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Acknowledgements
The authors wish to thank Ed Lewis for helpful discussions and comments on the manuscript. K.L.A. was supported by a grant from the Isaac Newton Trust and the Medical Research Council. The work was supported by a University of Nevada, Reno, Junior Faculty Research Grant awarded to R.A.D.
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Communicated by P. Simpson
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Arney, K.L., Bae, E., Olsen, C. et al. The human and mouse H19 imprinting control regions harbor an evolutionarily conserved silencer element that functions on transgenes in Drosophila . Dev Genes Evol 216, 811–819 (2006). https://doi.org/10.1007/s00427-006-0102-7
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DOI: https://doi.org/10.1007/s00427-006-0102-7