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.
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July 2016
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The reactions catalysed by enzymes associated with the TCA cycle (Krebs cycle) are commonly thought to operate in a full series of eight steps. However, under appropriate conditions in skeletal muscle and cells of immune system, the ‘cycle’ may be considered to operate in two separate parts. Firstly, in muscle, reactions of the right hand side of the cycle terminate at 2-oxoglutarate dehydrogenase, and the flux of carbon is shifted to the synthesis of glutamate and glutamine (for release into the bloodstream) via transaminases and glutamine synthetase respectively. Secondly, in immune cells such as lymphocytes, neutrophils and macrophages, glutamine may be converted to 2-oxoglutarate where it is metabolised by reactions of the left hand side of the TCA cycle where carbon may leave the cycle as malate or oxaloacetate, being subsequently converted to pyruvate (and lactate), or aspartate respectively. Image adapted from: Newsholme, E.A., Newsholme, P. and Curi, R. (1987) The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns. Biochem. Soc. Symp. 54, 145–162. For further details please see pp. 1845–1857. Image kindly provided by Philip Newsholme. - PDF Icon PDF LinkFront Matter
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Research Article|
June 28 2016
Transcription factors YY1, Sp1 and Sp3 modulate dystrophin Dp71 gene expression in hepatic cells
Katia Peñuelas-Urquides;
Katia Peñuelas-Urquides
1
*Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México
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Carolina Becerril-Esquivel;
Carolina Becerril-Esquivel
1
*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
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Laura C. Mendoza-de-León;
Laura C. Mendoza-de-León
*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
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Beatriz Silva-Ramírez;
Beatriz Silva-Ramírez
‡Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México
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José Dávila-Velderrain;
José Dávila-Velderrain
§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
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Bulmaro Cisneros;
Bulmaro Cisneros
¶Departamento de Genética y Biología Molecular Unidad Zacatenco, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City 07360, México
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Mario Bermúdez de León
Mario Bermúdez de León
2
*Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey 64720, Nuevo León, México
2To whom correspondence should be addressed (email mario.bermudez@imss.gob.mx).
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Publisher: Portland Press Ltd
Received:
February 25 2016
Revision Received:
April 22 2016
Accepted:
May 03 2016
Accepted Manuscript online:
May 03 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (13): 1967–1976.
Article history
Received:
February 25 2016
Revision Received:
April 22 2016
Accepted:
May 03 2016
Accepted Manuscript online:
May 03 2016
Citation
Katia Peñuelas-Urquides, Carolina Becerril-Esquivel, Laura C. Mendoza-de-León, Beatriz Silva-Ramírez, José Dávila-Velderrain, Bulmaro Cisneros, Mario Bermúdez de León; Transcription factors YY1, Sp1 and Sp3 modulate dystrophin Dp71 gene expression in hepatic cells. Biochem J 1 July 2016; 473 (13): 1967–1976. doi: https://doi.org/10.1042/BCJ20160163
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