Abstract:
:The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreas development and in beta-cell function. Upstream sequences of the gene up to about -6 kb show islet-specific activity in transgenic mice. Attempts to identify functional regulatory elements involved in the controlled expression of the pdx-1 gene led to the identification of distinct distal beta-cell-specific enhancers in human and rat genes. Three additional sequences, conserved between the mouse and the human 5'-flanking regions, two of which are also found in the chicken gene, conferred beta-cell-specific expression on a reporter gene, albeit to different extents. A number of transcription factors binding to and modulating the transcriptional activity of the regulatory elements were identified, such as hepatocyte nuclear factor (HNF)-3beta, HNF-1alpha, SP1/3, and, interestingly, PDX-1 itself. A fourth conserved region was localized to the proximal promoter around an E-box motif and was found to bind members of the upstream stimulatory factor (USF) family of transcription factors. We postulate that disruption of pdx-1 cis-acting regulatory sequences and/or mutations or functional impairment of transcription factors controlling the expression of the gene can lead to diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Melloul D,Marshak S,Cerasi Edoi
10.2337/diabetes.51.2007.s320subject
Has Abstractpub_date
2002-12-01 00:00:00pages
S320-5eissn
0012-1797issn
1939-327Xjournal_volume
51 Suppl 3pub_type
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