ARP1 interacts with the 5' flanking region of the coagulation factor VII gene.
Factor (F)VII plays a critical role in initiation of coagulation. Several segments within the 5' flanking region of the FVII gene were previously demonstrated to recognize hepatic nuclear proteins, but few have been identified. To identify a regulatory protein binding the nuclear hormone response region (-237 to -200) of the FVII 5' flanking region and demonstrate that the interaction is functional. Electrophoretic mobility shift assays and mutation analysis showed that ARP1, an orphan nuclear hormone receptor, interacted with two regions of the FVII 5' flanking region, the hepatic nuclear factor 4 binding region (-77 to -47) and the nuclear hormone response region (-237 to -200). Transfection experiments demonstrated that reporter gene expression was decreased from vectors including the nuclear hormone response segment compared with that containing only the minimal promoter between positions -109 and +1, and that ARP1 also repressed expression through an interaction with the minimal promoter. These data indicate a role for ARP1 in transcriptional modulation of the FVII gene.
Carew
J A
JA
VA Boston Healthcare System, Building 3, Room 2A106(151), 1400 VFW Parkway, West Roxbury, MA 02132, USA. josephine_carew@hms.harvard.edu
Jackson
A A
AA
Bauer
K A
KA
D024506:5' Flanking Region / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D005167:Factor VII / Q000235:genetics*; D017930:Genes, Reporter; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics; D011987:Receptors, Steroid; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D005167:Factor VII; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014157:Transcription Factors; C403128:MLX protein, human; C095569:NR2F2 protein, human