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Department of Pediatrics, University of Cincinnati College of Medicine, and Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Submitted 21 March 2006 ; accepted in final form 7 June 2006
Deletion analysis of the human growth hormone variant (GHV) promoter in transient transfection studies in BeWo choriocarcinoma and HepG2 cells indicated that the region extending from nt 158/+57 retained full transcriptional activity. DNase I footprint analysis of the fragment revealed a protected region at nt 82/77, which is in a putative FOXF1/FOXF2 binding site. Supershift assays using an antiserum to human FOXF1 demonstrated that the protected region binds FOXF1. Overexpression of FOXF1 in BeWo and HepG2 cells induced the GHV promoter, whereas overexpression of FOXF2 was without effect. Mutagenesis of the FOXF1/FOXF2 site reduced basal promoter activity by 5060% and markedly attenuated transactivation of the promoter by FOXF1. These studies indicate that FOXF1 induces GHV expression by interaction with a FOXF1/FOXF2 cis-element in the proximal promoter.
forkhead box F1; placenta; transcription; promoter activity
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