Pax6 and Pdx1 form a functional complex on the rat somatostatin gene upstream enhancer.

Abstract:

:The somatostatin upstream enhancer (SMS-UE) is a highly complex enhancer element. The distal A-element contains overlapping Pdx1 and Pbx binding sites. However, a point mutation in the A-element that abolishes both Pdxl and Pbx binding does not impair promoter activity. In contrast, a point mutation that selectively eliminates Pdx1 binding to a proximal B-element reduces the promoter activity. The B-element completely overlaps with a Pax6 binding site, the C-element. A point mutation in the C-element demonstrates that Pax6 binding is essential for promoter activity. Interestingly, a block mutation in the A-element reduces both Pax6 binding and promoter activity. In heterologous cells, Pdx1 potentiated Pax6 mediated activation of a somatostatin reporter. We conclude that the beta/delta-cell-specific activity of the SMS-UE is achieved through simultaneous binding of Pdx1 and Pax6 to the B- and C-elements, respectively. Furthermore, the A-element appears to stabilise Pax6 binding.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Andersen FG,Jensen J,Heller RS,Petersen HV,Larsson LI,Madsen OD,Serup P

doi

10.1016/s0014-5793(99)00144-1

keywords:

subject

Has Abstract

pub_date

1999-02-26 00:00:00

pages

315-20

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(99)00144-1

journal_volume

445

pub_type

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