Identification and regulation of tissue-specific cis-acting elements associated with the human AP-2alpha gene.
Mice lacking transcription factor AP-2alpha exhibit defects in the formation of the head, body wall, heart, neural tube, eye, and limbs, reflecting important sites of AP-2alpha expression in the developing embryo. AP-2alpha is also expressed in the postnatal mammary gland and has been linked to tumor progression and defects in growth regulation in the breast. We have used a transgenic mouse approach to identify tissue-specific cis-acting sequences associated with expression of the human AP-2alpha gene. Our analysis indicates that multiple elements located throughout the gene contribute to expression in the trigeminal ganglia, spinal cord, mammary gland, and epidermis. A discrete cis-element located within the fifth intron is required for expression in the face and limbs, and we have derived a permanent line of AP-2alpha::lacZ transgenic mice to assess expression of this latter enhancer throughout morphogenesis. We also introduced this transgene into an AP-2alpha-null mouse background and detected subtle alterations of its expression within the progress zone and apical ectodermal ridge of the forelimbs. Similar changes in lacZ expression were observed within the zeugopod, and these correlated with defects in radius condensation in AP-2alpha-knockout mice. Taken together, these findings indicate that cell:cell communication within the forelimb is altered in the absence of AP-2alpha and reveal novel regulatory potential for AP-2alpha in limb development.
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007438:Introns; D007763:Lac Operon; D017880:Limb Deformities, Congenital; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D014018:Tissue Distribution; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D019076:Transgenes
D004268:DNA-Binding Proteins; C493673:TFAP2A protein, human; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors