title: Transcription factors YY1, Sp1 and Sp3 modulate dystrophin Dp71 gene expression in hepatic cells.
abstract: Dystrophin Dp71, the smallest product encoded by the Duchenne muscular dystrophy gene, is ubiquitously expressed in all non-muscle cells. Although Dp71 is involved in various cellular processes, the mechanisms underlying its expression have been little studied. In hepatic cells, Dp71 expression is down-regulated by the xenobiotic β-naphthoflavone. However, the effectors of this regulation remain unknown. In the present study we aimed at identifying DNA elements and transcription factors involved in Dp71 expression in hepatic cells. Relevant DNA elements on the Dp71 promoter were identified by comparing Dp71 5'-end flanking regions between species. The functionality of these elements was demonstrated by site-directed mutagenesis. Using EMSAs and ChIP, we showed that the Sp1 (specificity protein 1), Sp3 (specificity protein 3) and YY1 (Yin and Yang 1) transcription factors bind to the Dp71 promoter region. Knockdown of Sp1, Sp3 and YY1 in hepatic cells increased endogenous Dp71 expression, but reduced Dp71 promoter activity. In summary, Dp71 expression in hepatic cells is carried out, in part, by YY1-, Sp1- and Sp3-mediated transcription from the Dp71 promoter.
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México.
authors.forename: Katia
authors.initials: K
authors.lastname: Peñuelas-Urquides
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, San Nicolás de los Garza 66451, Nuevo León, México.
authors.forename: Carolina
authors.initials: C
authors.lastname: Becerril-Esquivel
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, San Nicolás de los Garza 66451, Nuevo León, México.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Mendoza-de-León
authors.affiliation: Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Silva-Ramírez
authors.affiliation: Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City 04510, México Instituto de Ecología, Universidad Nacional Autónoma de México, Mexico City 04510, México.
authors.forename: José
authors.initials: J
authors.lastname: Dávila-Velderrain
authors.affiliation: Departamento de Genética y Biología Molecular Unidad Zacatenco, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City 07360, México.
authors.forename: Bulmaro
authors.initials: B
authors.lastname: Cisneros
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México mario.bermudez@imss.gob.mx.
authors.forename: Mario Bermúdez
authors.initials: MB
authors.lastname: de León
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D016329:Sp1 Transcription Factor; D050986:YY1 Transcription Factor; C085339:apo-dystrophin 1; D051705:Sp3 Transcription Factor
keywords: Dp71; Duchenne muscular dystrophy; hepatic cells; promoter; transcription factors