Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation.
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.
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
D J
DJ
Picketts
D P
DP
Lillicrap
C R
CR
Mueller
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003850:Deoxyribonuclease I; D005164:Factor IX / Q000235:genetics*; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011627:Puberty; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C063898:DBP protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C064567:factor IX Leyden; D005164:Factor IX; D004247:DNA; D003850:Deoxyribonuclease I