1: Oncogene. 2000 May 25;19(23):2786-90. 

The concerted regulatory functions of the transcription factors nuclear factor-1
and upstream stimulatory factor on a composite element in the promoter of the
hepatocyte growth factor gene.

Jiang JG, Gao B, Zarnegar R.

Department of Pathology, University of Pittsburgh, School of Medicine,
Pittsburth, Pennsylvania, PA 15261, USA.

Hepatocyte growth factor (HGF) is an important multifunctional cytokine whose
gene expression is regulated mainly at the transcriptional level. Previous
studies using transgenic mice as well as in vitro analyses showed that a
potential regulatory element(s) exists between -260 to -230 bp in the upstream
region of the HGF gene promoter. In the present study, we have discovered that
this region is a composite site through which members of the nuclear factor 1
(NF1) and upstream stimulatory factor (USF) families bind to and regulate HGF
gene transcription. Gel mobility shift and supershift assays revealed that USF
and NF1 have high binding affinity for this region and that the binding sites of
the two different transcription factor families overlap. Functional studies
showed that NF1 suppresses HGF gene promoter activity and that USF has an
activating function. We found that the NF1/X and NF1/Red1 isoforms strongly
suppressed HGF promoter activity while the NF1/L variant had no obvious effects.
USF1, but not USF2, of the USF family stimulated HGF gene promoter activity.
More interestingly, during liver regeneration after partial hepatectomy, a
process which activates the HGF gene, we noted that the binding activity of USF
to the HGF promoter element increased while that of NF1 decreased. These data
provide insight into the molecular mechanisms that govern HGF gene
transcription. Oncogene (2000).

PMID: 10851080 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------