Hox genes encode homeodomain-containing transcription factors that specify positional identity along body axes during animal embryogenesis. Correct spatially and temporally restricted expression of Hox genes is critical for normal embryonic development. The alteration of Hox gene expression may result in homeotic transformation or malformation of the embryo. / Using transgenic assays, we found that a previously mapped 5' retinoic acid response element (RARE) was not required for Hoxd4 gene expression in the central nervous system (CNS), but contributed to a 5' mesodermal enhancer. Neural and mesodermal enhancer activity of the gene were mapped to a 3' 4 kb region (region A). Removal of this region virtually abolished Hoxd4 expression in the CNS and posterorized expression in the somitic mesoderm by one somite. Further deletional analysis of the neural enhancer led to the identification of a 3' RARE. Mutation of this element virtually abolished transgene expression in the CNS. Analysis of permanent transgenic lines showed that this element was required not only for the initiation but also for the maintenance of Hoxd4 expression in the neural tube. In addition, this element is required for the Hoxd4 response to retinoic acid (RA). The second regulatory element we identified (TTTTCTG) is 2 bp downstream to the 3' RARE. It resembles a CDX binding site, but failed to interact with human CDX1 protein. Mutation of this site posteriorized transgene expression in the CNS. Although other regions required for murine Hoxd4 expression in the CNS were also mapped, our results suggest that Hoxd4 lacks an autoregulatory element (ARE). This is in contrast to the regulation of Hoxb4, where expression is initiated by the conserved RARE and subsequently maintained by an ARE. Together with other findings, this suggests that Hox genes sharing similar expression pattern may be regulated in a diverged manner.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36858 |
| Date | January 2000 |
| Creators | Zhang, Feng, 1965- |
| Contributors | Featherstone, Mark S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001770389, proquestno: NQ69954, Theses scanned by UMI/ProQuest. |
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