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Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation

Nature Genetics volume 3, pages 175–179 (1993)Cite this article

Abstract

Haemophilia B Leyden is characterized by low childhood levels of factor IX which gradually increase after puberty, eventually resulting in a return to health. The disease is the result of single nucleotide substitutions within a 40 bp region encompassing the major transcriptional start site. We have characterized transcription factor binding sites within the factor IX promoter. Five sites were identified and a Leyden mutation at nucleotide −5 was shown to interfere with the binding of proteins to one of three newly identified sites. The correlation between the post–pubertal recovery of these mutants and the induction of the transcription factor DBP led us to the discovery of a synergistic interaction between DBP and C/EBP responsible for the recovery of normal transcriptional activity of the −5 mutant promoter and may play a role in the resolution of other Leyden mutants.

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Authors and Affiliations

  1. Department of Pathology, Queen's University, Kingston, Ontario, Canada, K7L 3N6

    David J. Picketts, David P. Lillicrap & Christopher R. Mueller

  2. Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada, K7L 3N6

    Christopher R. Mueller

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  1. David J. Picketts
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  2. David P. Lillicrap
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  3. Christopher R. Mueller
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Picketts, D., Lillicrap, D. & Mueller, C. Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation. Nat Genet 3, 175–179 (1993). https://doi.org/10.1038/ng0293-175

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