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Effect of elongation factor 1α promoter and SUMF1 over in vitro expression of N-acetylgalactosamine-6-sulfate sulfatase

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Abstract

Morquio A is an autosomal recessive disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to the lysosomal accumulation of keratan-sulfate and chondroitin-6-sulfate. We evaluated in HEK293 cells the effect of the cytomegalovirus immediate early enhancer/promoter (CMV) or the elongation factor 1α (EF1α) promoters, and the coexpression with the sulfatase modifying factor 1 (SUMF1) on GALNS activity. Four days postransfection GALNS activity in transfected cells with CMV-pIRES-GALNS reached a plateau, whereas in cells transfected with EF1α-pIRES-GALNS continued to increase until day 8. Co-transfection with pCXN-SUMF1 showed an increment up to 2.6-fold in GALNS activity. Finally, computational analysis of transcription factor binding-sites and CpG islands showed that EF1α promoter has long CpG islands and high-density binding-sites for Sp1 compared to CMV. These results show the advantage of the SUMF1 coexpression on GALNS activity and indicate a considerable effect on the expression stability using EF1α promoter compared to CMV.

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Acknowledgments

This work was supported in part by the Pontificia Universidad Javeriana’s Genomic Initiative (ID 000950). CJAD received a scholarship from Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología—COLCIENCIAS. We would like to thank Johanna Luna and Rocio Cuaspa for their assistance.

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Authors and Affiliations

  1. Instituto de Errores Innatos del Metabolismo, Pontificia Universidad Javeriana, Cra 7 No. 43–82 Building 53, Room 305A, Bogota D.C., Colombia

    Carlos J. Alméciga-Díaz, Maria A. Rueda-Paramo, Angela J. Espejo, Olga Y. Echeverri & Luis A. Barrera

  2. Department of Pediatrics, Saint Louis University, St Louis, MO, 63104, USA

    Adriana Montaño & Shunji Tomatsu

Authors
  1. Carlos J. Alméciga-Díaz
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  2. Maria A. Rueda-Paramo
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  3. Angela J. Espejo
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  4. Olga Y. Echeverri
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  5. Adriana Montaño
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  6. Shunji Tomatsu
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  7. Luis A. Barrera
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Correspondence to Luis A. Barrera.

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Carlos J. Alméciga-Díaz and Maria A. Rueda-Paramo contributed equally to this work.

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Alméciga-Díaz, C.J., Rueda-Paramo, M.A., Espejo, A.J. et al. Effect of elongation factor 1α promoter and SUMF1 over in vitro expression of N-acetylgalactosamine-6-sulfate sulfatase. Mol Biol Rep 36, 1863–1870 (2009). https://doi.org/10.1007/s11033-008-9392-3

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