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doi: 10.1242/10.1242/dev.00151

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Evolutionary conserved sequences are required for the insulation of the vertebrate Hoxd complex in neural cells

Marie Kmita, Basile Tarchini, Denis Duboule^* and Yann Hérault

Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
Present address: Molecular and Experimental Genetics, FRE2358, CNRS, Institut de Transgénose, rue de la Férollerie, 3B, 45071, Orléans cedex 2, France

^* Author for correspondence (e-mail: denis.duboule{at}zoo.unige.ch)

Accepted 20 June 2002

Transcriptional regulation of vertebrate Hox genes involves enhancer sequences located either inside or outside the gene clusters. In the mouse Hoxd complex, for example, series of contiguous genes are coordinately controlled by regulatory sequences located at remote distances. However, in different cellular contexts, Hox genes may have to be insulated from undesirable external regulatory influences to prevent ectopic gene activation, a situation that would likely be detrimental to the developing embryo. We show the presence of an insulator activity, at one extremity of the Hoxd complex, that is composed of at least two distinct DNA elements, one of which is conserved throughout vertebrate species. However, deletion of this element on its own did not detectably affect Hoxd gene expression, unless another DNA fragment located nearby was removed in cis. These results suggest that insulation of this important gene cluster relies, at least in part, upon a sequence-specific mechanism that displays some redundancy.

Key words: Insulator, Gene regulation, Hox complex, Mouse

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