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
Jg. Jiang et al., 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, ONCOGENE, 19(23), 2000, pp. 2786-2790
Hepatocyte growth factor (HGF) is an important multifunctional cytokine who
se gene expression is regulated mainly at the transcriptional level, Previo
us 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 upst
ream region of the HGF gene promoter. In the present study, me have discove
red that this region is a composite site through which members of the nucle
ar factor 1 (NF1) and upstream stimulatory factor (USF) families bind to an
d regulate HGF gene transcription. Gel mobility shift and supershift assays
revealed that USF and NF1 have high binding affinity for this region and t
hat the binding sites of the two different transcription factor families ov
erlap. Functional studies showed that NF1 suppresses HGF gene promoter acti
vity and that USF has an activating function, We found that the NF1/X and N
F1/Red1 isoforms strongly suppressed HGF promoter activity while the NF1/L
variant had no obvious effects. USF1, but not USF2, of the USF family stimu
lated HGF gene promoter activity, More interestingly, during liver regenera
tion after partial hepatectomy, a process which activates the HGF gene, we
noted that the binding activity of USF to the HGF promoter element increase
d while that of NF1 decreased. These data provide insight into the molecula
r mechanisms that govern HGF gene transcription.