Comparison of the 5'-flanking sequences of the human and bovine von Willebrand factor-encoding genes reveals alternation of highly homologous domains with species-specific Alu-type repeats

• Published in: Gene Vol. 167; no. 1-2; pp. 291 - 295
• Main Authors: Janel, N, Schwachtgen, J-L, Bakhshi, M R, Barek, L, Meyer, D, Kerbiriou-Nabias, D
• Format: Journal Article
• Language: English
• Published: 01.01.1996
• ISSN: 0378-1119

von Willebrand factor (vWF), a multimeric glycoprotein important for hemostasis, is specifically synthesized in endothelial cells and in platelet precursors (megakaryocytes). Recent studies from two laboratories, including ours, were published regarding the cell-specific transcription of reporter genes controlled by the human (hu) vWF promoter in transfected bovine (bo) endothelial cells and cells of non-endothelialorigins. In order to verify that the regulatory domains previously characterized in the 5' region of hu vWF are also present in bo vWF, we have sequenced 1.9kb upstream from the cap site, plus five exons. The comparison of hu and bo exons two to five shows homology of 83% at thenucleotide (nt) level and 78% at the deduced amino-acid sequence level. The bovine and human exons one, which are non-coding and span 233 and 250bp, respectively, are only 64% homologous. In the first exon, potentially involved in endothelial-cell-specific transcription, the binding site for factor Sp1 is present in bo vWF, whereas the GATA sequence is replaced by a GACA sequence. The sequence corresponding to the human basal promoter, located between nt -89 and +19, is well conserved with 82% homology. However, the human TAATTA sequence (at nt -32) considered to be a TATA box, is replaced by TCATTA, and the CCAAT elementat nt -18 is replaced by CCTGT. Among domains involved in transcription, the negative regulatory domain located 5' from the core promoter is highly conserved. The bovine sequence upstream from the first ron can be aligned with the human sequence up to nt -656 which is located ina polymorphic poly(GT)18-26 sequence. At this site, the bovine DNA contains an insertion of 523bp which corresponds to a bovine Alu-type art2 repeat of 331bp flanked by bovine microsatellites. The art2 sequence is an Alu-type repeat in artiodactyls with at least 100000 copies inthe bovine genome. Upstream from this insertion, 368bp of the bovine sequence can be aligned with the human counterpart up to a 9-bp element which flanks an human Alu repeat which is absent from the bovine DNA. Upstream of the human Alu insertion and a duplicate of the 9-bp element, the two sequences are again homologous.