Id |
Subject |
Object |
Predicate |
Lexical cue |
TextSentencer_T1 |
0-145 |
Sentence |
denotes |
Two mutations in the promoter region of the human protein C gene both cause type I protein C deficiency by disruption of two HNF-3 binding sites. |
TextSentencer_T2 |
146-298 |
Sentence |
denotes |
Protein C is a vitamin K-dependent zymogen of a serine protease that inhibits blood coagulation by the proteolytic inactivation of factors Va and VIIIa. |
TextSentencer_T3 |
299-373 |
Sentence |
denotes |
Individuals affected with protein C deficiency are at risk for thrombosis. |
TextSentencer_T4 |
374-583 |
Sentence |
denotes |
Genetic analyses of affected individuals, to determine the cause of the protein C deficiency, revealed a large variety of mutations in the protein C gene, including several in the promoter region of this gene. |
TextSentencer_T5 |
584-794 |
Sentence |
denotes |
Comparison of the region around two of these mutations, A-32-->G and T-27-->A, with transcription factor consensus sequences suggested the presence of two overlapping and inversely oriented HNF-3 binding sites. |
TextSentencer_T6 |
795-975 |
Sentence |
denotes |
Direct evidence for the presence of the two HNF-3 binding sites in the protein C promoter was obtained using electrophoretic mobility shift assays and UV cross-linking experiments. |
TextSentencer_T7 |
976-1101 |
Sentence |
denotes |
These experiments revealed that HNF-3 can bind specifically to both putative HNF-3 sites in the wild-type protein C promoter. |
TextSentencer_T8 |
1102-1244 |
Sentence |
denotes |
Due to the T-27-->A mutation, one binding site is completely lost, while the other site still binds HNF-3, but with strongly reduced affinity. |
TextSentencer_T9 |
1245-1348 |
Sentence |
denotes |
As a consequence of the A-32-->G mutation, the protein C promoter loses all its HNF-3 binding capacity. |
TextSentencer_T10 |
1349-1482 |
Sentence |
denotes |
Transient transfection experiments demonstrated that the binding of HNF-3 to the protein C promoter is of physiological significance. |
TextSentencer_T11 |
1483-1641 |
Sentence |
denotes |
This followed from experiments in which the introduction of the A-32-->G or T-27-->A mutation resulted in a 4-5-fold reduced promoter activity in HepG2 cells. |
TextSentencer_T12 |
1642-1789 |
Sentence |
denotes |
Furthermore, transactivation of the wild-type protein C promoter construct with HNF-3 showed a 4-5-fold increased promoter activity in HepG2 cells. |
TextSentencer_T13 |
1790-1896 |
Sentence |
denotes |
In HeLa cells, significant wild-type promoter activity was only observed after transactivation with HNF-3. |
TextSentencer_T14 |
1897-2107 |
Sentence |
denotes |
When a promoter construct containing the T-->A mutation at position -27 was used, the transactivation potential of HNF-3 was 2-fold reduced in HepG2 cells, whereas in HeLa cells no transactivation was observed. |
TextSentencer_T15 |
2108-2241 |
Sentence |
denotes |
With the promoter construct containing the A-32-->G mutation, no transactivation by HNF-3 was found either in HepG2 or in HeLa cells. |
T1 |
0-145 |
Sentence |
denotes |
Two mutations in the promoter region of the human protein C gene both cause type I protein C deficiency by disruption of two HNF-3 binding sites. |
T2 |
146-298 |
Sentence |
denotes |
Protein C is a vitamin K-dependent zymogen of a serine protease that inhibits blood coagulation by the proteolytic inactivation of factors Va and VIIIa. |
T3 |
299-373 |
Sentence |
denotes |
Individuals affected with protein C deficiency are at risk for thrombosis. |
T4 |
374-583 |
Sentence |
denotes |
Genetic analyses of affected individuals, to determine the cause of the protein C deficiency, revealed a large variety of mutations in the protein C gene, including several in the promoter region of this gene. |
T5 |
584-794 |
Sentence |
denotes |
Comparison of the region around two of these mutations, A-32-->G and T-27-->A, with transcription factor consensus sequences suggested the presence of two overlapping and inversely oriented HNF-3 binding sites. |
T6 |
795-975 |
Sentence |
denotes |
Direct evidence for the presence of the two HNF-3 binding sites in the protein C promoter was obtained using electrophoretic mobility shift assays and UV cross-linking experiments. |
T7 |
976-1101 |
Sentence |
denotes |
These experiments revealed that HNF-3 can bind specifically to both putative HNF-3 sites in the wild-type protein C promoter. |
T8 |
1102-1244 |
Sentence |
denotes |
Due to the T-27-->A mutation, one binding site is completely lost, while the other site still binds HNF-3, but with strongly reduced affinity. |
T9 |
1245-1348 |
Sentence |
denotes |
As a consequence of the A-32-->G mutation, the protein C promoter loses all its HNF-3 binding capacity. |
T10 |
1349-1482 |
Sentence |
denotes |
Transient transfection experiments demonstrated that the binding of HNF-3 to the protein C promoter is of physiological significance. |
T11 |
1483-1641 |
Sentence |
denotes |
This followed from experiments in which the introduction of the A-32-->G or T-27-->A mutation resulted in a 4-5-fold reduced promoter activity in HepG2 cells. |
T12 |
1642-1789 |
Sentence |
denotes |
Furthermore, transactivation of the wild-type protein C promoter construct with HNF-3 showed a 4-5-fold increased promoter activity in HepG2 cells. |
T13 |
1790-1896 |
Sentence |
denotes |
In HeLa cells, significant wild-type promoter activity was only observed after transactivation with HNF-3. |
T14 |
1897-2107 |
Sentence |
denotes |
When a promoter construct containing the T-->A mutation at position -27 was used, the transactivation potential of HNF-3 was 2-fold reduced in HepG2 cells, whereas in HeLa cells no transactivation was observed. |
T15 |
2108-2241 |
Sentence |
denotes |
With the promoter construct containing the A-32-->G mutation, no transactivation by HNF-3 was found either in HepG2 or in HeLa cells. |