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Publication : Regulation of the Hoxb-8 gene: synergism between multimerized cis-acting elements increases responsiveness to positional information.

First Author  Charité J Year  1995
Journal  Dev Biol Volume  171
Issue  2 Pages  294-305
PubMed ID  7556914 Mgi Jnum  J:29038
Mgi Id  MGI:76563 Doi  10.1006/dbio.1995.1282
Citation  Charite J, et al. (1995) Regulation of the Hoxb-8 gene: synergism between multimerized cis-acting elements increases responsiveness to positional information. Dev Biol 171(2):294-305
abstractText  Hox genes play a key role in the specification of regional development in the vertebrate embryo. They are expressed in regionally restricted domains along the anterior-posterior axis, generally extending from a sharp rostral boundary toward the posterior end. We have studied the regulation of the murine Hoxb-8 gene in vivo using reporter constructs and found that 11 kb of genomic sequences upstream of Hoxb-8 confer a Hox-like pattern of expression on a lacZ reporter gene fused in-frame to the first exon of Hoxb-8. Reporter gene expression was detectable from early stages onwards, but reached rostral expression boundaries in mesoderm and neurectoderm that were more posterior than those of the endogenous gene. Within the upstream region, we have identified several cis-acting elements which are individually capable of driving regionally restricted expression in combination with the Hoxb-8 promoter, and we have investigated their relative contributions to the expression pattern. The results suggest that, in this experimental context, these upstream elements, as well as previously identified elements located within the Hoxb-8 gene, cooperate in setting the rostral expression boundaries. Furthermore, we show that multiple identical copies of cis-acting elements can cooperate, causing a pronounced anterior shift in the expression boundaries. This indicates that the rostral extent of expression is limited by the activity of a transcription factor binding to these elements and that this activity was, at some point in development, higher in precursors of more posterior structures than in precursors of anterior structures. This factor is thus very likely to be involved in the transduction of positional signals.
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