title: Alx4 binding to LEF-1 regulates N-CAM promoter activity.
abstract: During murine embryogenesis, expression of the paired-like homeodomain protein Alx4 is restricted to tissues whose development depends on the expression of lymphoid enhancer factor-1 (LEF-1). Given the defects seen in hair follicle development in both LEF-1 and Alx4 knockout and mutant animals and the overlapping expression patterns, we predicted that LEF-1 and Alx4 might form physical complexes. We demonstrate here the interaction between LEF-1 and Alx4. This interaction is mediated through a specific proline-rich domain in the N-terminal region of Alx4 and requires the DNA-binding domain (HMG-box) of LEF-1. We also demonstrate that LEF-1 and Alx4 can bind simultaneously to adjacent sites on the neural cell adhesion molecule (N-CAM) promoter and that this binding alters N-CAM promoter activity. Furthermore, when expressed in primary mammary stromal cells, Alx4 decreases the expression of endogenous N-CAM protein. These results reveal a potential mechanism that gives rise to mesenchymal-specific activities of LEF-1.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1A8, Canada.
authors.forename: Kata
authors.initials: K
authors.lastname: Boras
authors.forename: Paul A
authors.initials: PA
authors.lastname: Hamel
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C416676:ALX4 protein, human; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D019006:Neural Cell Adhesion Molecules; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors