Identification of evolutionarily invariant sequences in the protein C gene promoter.
Recent studies on human protein C gene expression have revealed the presence of three transcription factor binding sites in close proximity to the transcription start site. Binding sites for the liver-enriched hepatocyte nuclear factors 1 and 3 (HNF-1 and HNF-3, respectively) are located immediately upstream of the transcription start site, whereas just downstream of the start site a presently unidentified transcription factor may bind. To identify other candidate transcription factor binding sites in the protein C promoter, we studied the promoter sequence identity in a number of evolutionarily close and more distant species: Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Homo sapiens, Cebus apella, Macaca mulatta, Callithrix jacchus, Papio hamadryas, Macaca fascicularis, and Rattus norvegicus. This analysis showed that a high degree of identity (78%) exists among the different primates. Comparison of the primate consensus sequence with the Rattus norvegicus protein C promoter sequence revealed the presence of seven identical regions (I to VII). Two of these regions overlap with established regulatory sequences for HNF-3 and HNF-1 (region VI) and for PCE-1 (region VII), respectively. The functional importance and the transcription factors that may bind to the other five identical regions are now to be determined.
Spek
C A
CA
Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden, The Netherlands.
Bertina
R M
RM
Reitsma
P H
PH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011323:Primates / Q000235:genetics; D011401:Promoter Regions, Genetic; D011486:Protein C / Q000235:genetics*; D051381:Rats; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
D017931:DNA Primers; D011486:Protein C; D014157:Transcription Factors; D004247:DNA