H. Watada et al., INVOLVEMENT OF THE HOMEODOMAIN-CONTAINING TRANSCRIPTION FACTOR PDX-1 IN ISLET AMYLOID POLYPEPTIDE GENE-TRANSCRIPTION, Biochemical and biophysical research communications, 229(3), 1996, pp. 746-751
The AT-rich eis-motif A elements of the insulin gene promoter contribu
te to directing the gene's expression to pancreatic beta-cells, bound
by a homeodomin-containing transcription factor, PDX-1/IPF1/STF-1/IDX-
1. The islet amyloid polypeptide (IAPP; amylin) gene, which is also ex
pressed in limited tissues such as pancreatic beta- and delta-cells, c
ontained similar AT-rich sequences in its regulatory sequences. To und
erstand the molecular basis of IAPP gene regulation, we evaluated the
possible physiological significance of the motif in human IAPP gene re
gulation. All of the three typical A element-like sequences that match
ed the CT-box consensus (AT-1, -207/-202; AT-2, -154/-142; and AT-3, -
88/-83) were shown to bind specifically to a nuclear factor in the bet
a-cell-derived MIN6 cells, which was subsequently identified immunolog
ically as the insulin gene transcription factor PDX-1. When the promot
er activity was examined in MIN6 cells, the disruption of AT-1 or AT-3
but not of AT-2 caused a marked reduction in the IAPP gene promoter.
Thus, despite the observation that ll the three A element-like regions
could bind to PDX-1, the AT-2 site may not be involved in mediating t
he PDX-1 action in vivo. These observations suggest the involvement of
PDX-1 in human IAPP gene regulation, which seems to be mediated throu
gh at least two A element-like cis-motifs in the gene promoter. (C) 19
96 Acamdemic Press