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Study of Long-Distance Functional Interactions between Su(Hw) Insulators That Can Regulate Enhancer-Promoter Communication in Drosophila melanogaster

Ekaterina Savitskaya,^1,2, Larisa Melnikova,^1, Margarita Kostuchenko,¹ Elena Kravchenko,¹ Ekaterina Pomerantseva,¹ Tatiana Boikova,¹ Darya Chetverina,¹ Aleksander Parshikov,¹ Polyna Zobacheva,¹ Elena Gracheva,^1, Alexander Galkin,³ and Pavel Georgiev^1*

Department of the Control of Genetic Processes, Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia,¹ Biomedical Center of Oslo University, Moscow 119334, Russia,² Institute of Agricultural Biotechnology, Moscow 127550, Russia³

Received 17 June 2005/ Returned for modification 15 July 2005/ Accepted 3 November 2005

The Su(Hw) insulator found in the gypsy retrotransposon is the most potent enhancer blocker in Drosophila melanogaster. However, two such insulators in tandem do not prevent enhancer-promoter communication, apparently because of their pairing interaction that results in mutual neutralization. Furthering our studies of the role of insulators in the control of gene expression, here we present a functional analysis of a large set of transgenic constructs with various arrangements of regulatory elements, including two or three insulators. We demonstrate that their interplay can have quite different outcomes depending on the order of and distance between elements. Thus, insulators can interact with each other over considerable distances, across interposed enhancers or promoters and coding sequences, whereby enhancer blocking may be attenuated, cancelled, or restored. Some inferences concerning the possible modes of insulator action are made from collating the new data and the relevant literature, with tentative schemes illustrating the regulatory situations in particular model constructs.

These authors contributed equally to this work.

Present address: Department of Biology, Washington University, St. Louis, MO 63130.

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