In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries

Gerard, Matthieu; Chen, Jia-Yang; Gronemeyer, Hinrich; Chambon, Pierre; Duboule, Denis; Zakany, Jozsef

doi:10.1101/gad.10.18.2326

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Title		In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries
Authors		Gerard, Matthieu Chen, Jia-Yang Gronemeyer, Hinrich Chambon, Pierre Duboule, Denis Zakany, Jozsef
Published in		Genes & development. 1996, vol. 10, no. 18, p. 2326-2334
Abstract		Vertebrate Hox genes are required for the proper organization of structures along the rostrocaudal axis. Hoxd-11 is expressed in the posterior part of the embryo, up to the level of prevertebra 27, and its expression boundary is reproduced by a Hoxd-11/lacZ transgene. Expression of this transgene anterior to prevertebra 27 is prevented by the silencing activity of a cis-acting element, region IX. Using transgenic mice, we show that Hoxd-11 repression by region IX is necessary to position the sacrum properly. This silencing activity depends on phylogenetically conserved sequences able to bind in vitro retinoic acid receptors and COUP-TFs. ES cells were used to generate mice carrying a subtle mutation that abolishes binding of nuclear receptors to region IX. Mutant mice display an anterior shift of their lumbosacral transition inherited as a codominant trait. In mutant embryos, expression of both Hoxd-11 and Hoxd-10 mRNAs in the prevertebral column is anteriorized. These results illustrate the sharing, in cis, of a single regulatory element in order to establish the expression boundaries of two neighboring Hoxd genes.
Keywords		ES cells — Mouse development — HoxD complex — Regulatory mutation — Nuclear receptors
Identifiers		DOI: 10.1101/gad.10.18.2326 PMID: 8824591
Full text		Article (Published version) (12.4 MB) - Limited access to UNIGE
Structures		Faculté des sciences / Section de biologie / Département de génétique et évolution
Citation (ISO format)		GERARD, Matthieu et al. In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries. In: Genes & development, 1996, vol. 10, n° 18, p. 2326-2334. doi: 10.1101/gad.10.18.2326 https://archive-ouverte.unige.ch/unige:84853