An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins.

Chen J, Ruley HE
J Biol Chem. 1998 273 (38): 24670-5

PMID: 9733765 · DOI:10.1074/jbc.273.38.24670

In the hindbrain of the mouse embryo, there is often coincident rhombomere-restricted expression of Eph receptor tyrosine kinases and Hox homeobox genes, raising the possibility of regulatory interactions. In this paper, we have identified cis-acting regulatory sequences of the EphA2 (Eck) gene, which direct node and hindbrain-specific expression in transgenic embryos. An 8-kilobase region of mouse genomic DNA element was sufficient to drive rhombomere 4 (r4)-specific expression while conferring patchy expression in the node. Further analysis localized the rhombomere-specific enhancer to a 0.9-kilobase sequence. This element contains multiple Hox-Pbx consensus binding sites that bind to both HOXA1/Pbx1 and HOXB1/Pbx1 proteins in vitro. Co-expression of either HOXA1 or HOXB1 with Pbx1 transactivated EphA2 enhancer-dependent reporter gene expression. These results, together with observations of reduced EphA2 expression in hoxa1 and hoxb1 double mutant mice, suggest that expression of EphA2 gene in rhombomere 4 is directly regulated by Hoxa1 and Hoxb1 homeobox transcription factors.

MeSH Terms (22)

Animals Base Sequence Binding Sites Cell Line Consensus Sequence COS Cells DNA Primers Embryonic and Fetal Development Enhancer Elements, Genetic Female Gene Expression Regulation, Developmental Homeodomain Proteins Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Molecular Sequence Data Polymerase Chain Reaction Repetitive Sequences, Nucleic Acid Rhombencephalon Transcription Factors Transfection

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