YY1 acts as a transcriptional activator of Hoxa5 gene expression in mouse organogenesis.
The Hox gene family encodes homeodomain-containing transcriptional regulators that confer positional information to axial and paraxial tissues in the developing embryo. The dynamic Hox gene expression pattern requires mechanisms that differentially control Hox transcription in a precise spatio-temporal fashion. This implies an integrated regulation of neighbouring Hox genes achieved through the sharing and the selective use of defined enhancer sequences. The Hoxa5 gene plays a crucial role in lung and gut organogenesis. To position Hoxa5 in the regulatory hierarchy that drives organ morphogenesis, we searched for cis-acting regulatory sequences and associated trans-acting factors required for Hoxa5 expression in the developing lung and gut. Using mouse transgenesis, we identified two DNA regions included in a 1.5-kb XbaI-XbaI fragment located in the Hoxa4-Hoxa5 intergenic domain and known to control Hoxa4 organ expression. The multifunctional YY1 transcription factor binds the two regulatory sequences in vitro and in vivo. Moreover, the mesenchymal deletion of the Yy1 gene function in mice results in a Hoxa5-like lung phenotype with decreased Hoxa5 and Hoxa4 gene expression. Thus, YY1 acts as a positive regulator of Hoxa5 expression in the developing lung and gut. Our data also support a role for YY1 in the coordinated expression of Hox genes for correct organogenesis.
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec, Canada; Centre de recherche du Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Québec, Canada.
Félix-Antoine
FA
Bérubé-Simard
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec, Canada; Centre de recherche du Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Québec, Canada.
Christelle
C
Prudhomme
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec, Canada; Centre de recherche du Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Québec, Canada.
Lucie
L
Jeannotte
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018507:Gene Expression Regulation, Developmental; D023061:Gene Order; D018390:Gene Targeting; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D014157:Transcription Factors; D050986:YY1 Transcription Factor / Q000378:metabolism*
D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor