Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3β transcription factors mediate β-cell-specific expression

S. Marshak, E. Benshushan, M. Shoshkes, L. Havin, E. Cerasi, D. Melloul*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

The PDX-1 transcription factor plays a key role in pancreatic development and in the regulation of the insulin gene in the adult β cell. As its functions appear to be similar in humans and mice, we analyzed the functional conservation of homologous sequences important for the maintenance and the cell-specific regulation of the pdx-1 gene. Apart from the proximal promoter region, three highly homologous (PH1 to PH3) sequences were apparent in the human and mouse 5' flanking regions of the gene. By transient transfections in β and non-β cells, we show that mainly PH1 and PH2 preferentially confer β-cell-specific activation on a heterologous promoter. DNase I footprinting and binding analyses revealed that both bind to and are transactivated by hepatocyte nuclear factor 3β (HNF-3β). Furthermore, the PH1 enhancer element also binds the PDX-1 transcription factor itself, which acts cooperatively with adjacent HNF-3β to regulate its transcriptional potency. This finding suggests a possible autoregulatory loop as a mechanism for PDX-1 to control its own expression.

Original languageAmerican English
Pages (from-to)7583-7590
Number of pages8
JournalMolecular and Cellular Biology
Volume20
Issue number20
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Dive into the research topics of 'Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3β transcription factors mediate β-cell-specific expression'. Together they form a unique fingerprint.

Cite this