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Molecular and Cellular Biology, February 2005, p. 1389-1401, Vol. 25, No. 4
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.4.1389-1401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cdx Protein Interaction with Hoxa5 Regulatory Sequences Contributes to Hoxa5 Regional Expression along the Axial Skeleton

Sébastien Tabariès,^1, Jérôme Lapointe,^1, Terri Besch,² Marcelle Carter,¹ John Woollard,² Christopher K. Tuggle,² and Lucie Jeannotte^1*

Centre de Recherche en Cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, Québec, Canada,¹ Department of Animal Science, Iowa State University, Ames, Iowa²

Received 24 June 2004/ Returned for modification 24 September 2004/ Accepted 18 November 2004

Hox gene functions are intimately linked to correct developmental expression of the genes. The identification of cis-acting regulatory sequences and their associated trans-acting factors constitutes a key step in deciphering the mechanisms underlying the correct positioning of the functional domain of Hox genes along the anterior-posterior axis. We have identified DNA elements driving Hoxa5 regionalized expression in mice, using the 2.1-kb mesodermal enhancer (MES) localized in Hoxa5 3' flanking sequences as a starting point. The MES sequence comprises regulatory elements targeting Hoxa5 expression in the limbs, the urogenital and gastrointestinal tracts, and the cervical-upper thoracic region of the prevertebral column. A 164-bp DNA fragment within the MES caudally restricts Hoxa5 expression at the level of prevertebra 10, corresponding to the posterior limit of its functional domain. Cdx proteins directly bind to this element in vitro via two conserved sites. Preventing Cdx binding by mutating the sites causes caudal expansion of the transgene expression domain. Of all three murine Cdx proteins that bind this element in vitro, Cdx4 has emerged as a potential regional posterior repressor of Hoxa5 expression. The restrictive control provided by Cdx interactions with Hoxa5 regulatory sequences may be one of the critical events in cervicothoracic axial specification.

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* Corresponding author. Mailing address: Centre de Recherche de L'Hôtel-Dieu de Québec, 9 rue McMahon, Québec, QC G1R 2J6, Canada. Phone: (418) 525-4444, ext. 15552. Fax: (418) 691-5439. E-mail: lucie.jeannotte{at}crhdq.ulaval.ca.

S.T. and J.L. contributed equally to this work.

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Molecular and Cellular Biology, February 2005, p. 1389-1401, Vol. 25, No. 4
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.4.1389-1401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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