ArticleMolecular and cellular biology1996
The human clotting factor VIII cDNA contains an autonomously replicating sequence consensus- and matrix attachment region-like sequence that binds a nuclear factor, represses heterologous gene expression, and mediates the transcriptional effects of sodium butyrate.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 35 citations in OpenAlex.
- Heterogeneity and reciprocity of FVIII and VWF expression, and the response to shear stress in cultured human endothelial cells.Journal of thrombosis and haemostasis : JTH · 2022Article
- Defining the Optimal FVIII Transgene for Placental Cell-Based Gene Therapy to Treat Hemophilia A.Molecular therapy. Methods & clinical development · 2020Article
- Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs.Experimental & molecular medicine · 2019Article
- Stable high-level expression of factor VIII in Chinese hamster ovary cells in improved elongation factor-1 alpha-based system.BMC biotechnology · 2017Article
- Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.Gene therapy · 2013Article
- Blood Clotting Factor VIII: From Evolution to Therapy.Acta naturae · 2013Article
- Kaposi's Sarcoma-Associated Herpesvirus Genome Replication, Partitioning, and Maintenance in Latency.Frontiers in microbiology · 2012Article
- Prospects for the use of artificial chromosomes and minichromosome-like episomes in gene therapy.Journal of biomedicine & biotechnology · 2010Article
- Analysis of factor VIII mediated suppression of lentiviral vector titres.Gene therapy · 2008Article
- Intracellular trafficking of factor VIII to von Willebrand factor storage granules.The Journal of clinical investigation · 1998Article
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7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Expression of the human blood-clotting factor VIII (FVIII) cDNA is hampered by the presence of sequences located in the coding region that repress transcription. We have previously identified a 305-bp fragment within the FVIII cDNA that is involved in the repression (R.C. Hoeben, F.J. Fallaux, S.J. Cramer, D.J.M. van den Wollenberg, H. van Ormondt, E. Briet, and A.J. van der Eb, Blood 85:2447-2454, 1995). Here, we show that this 305-bp region of FVIII cDNA contains sequences that resemble the yeast (Saccharomyces cerevisiae) autonomously replicating sequence consensus. Two of these DNA elements coincide with AT-rich sequences that are often found in matrix attachment regions or scaffold-attached regions. One of these elements, consisting of nucleotides 1569 to 1600 of the FVIII cDNA (nucleotide numbering is according to the system of Wood et al. (W.I. Wood, D.J. Capon, C.C. Simonsen, D.L. Eaton, J. Gitschier, D. Keyt, P.H. Seeburg, D.H. Smith, P. Hollingshead, K.L. Wion, et al., Nature [London] 312:330-337,1984), binds a nuclear factor in vitro but loses this capacity after four of its base pairs have been changed. A synthetic heptamer of this segment can repress the expression of a chloramphenicol acetyltransferase (CAT) reporter gene and also loses this capacity upon mutation. Furthermore, we demonstrate that repression by FVIII sequences can be relieved by sodium butyrate. We demonstrate that the synthetic heptamer (FVIII nucleotides 1569 to 1600), when placed upstream of the Moloney murine leukemia virus long terminal repeat promoter that drives the CAT reporter, can render the CAT reporter inducible by butyrate. This effect was absent when the same element was mutated. The stimulatory effect of butyrate could not be attributed to butyrate-responsive elements in the studied long terminal repeat promoters. Our data provide a functional characterization of the sequences that repress expression of the FVIII cDNA. These data also suggest a link between transcriptional repression by FVIII cDNA elements and the stimulatory effect of butyrate on FVIII cDNA expression.
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