Conserved transcriptional regulatory domains of the pdx-1 gene.
The pancreas and duodenum homeobox protein 1 (PDX-1) homeodomain-containing transcription factor affects both pancreatic endocrine cell development and adult islet beta-cell function. Cell-type-specific expression is controlled by sequences 5' flanking the pdx-1 gene transcription start site. One principal control region is located roughly between -2800 and -1600 bp and spans three conserved, distinct, and functionally important subdomains, termed areas I, II, and III. In this study, we found that an upstream control region in the rat pdx-1 gene located between -6200 and -5670 bp is also present in the mouse, chicken, and human genes. This region is capable of independently directing pancreatic beta-cell-selective reporter gene expression and potentiating area I/II-driven activity. This newly recognized conserved subdomain has been termed area IV. The islet-enriched forkhead box A2 (FoxA2), NK2 homeobox 2.2 (Nkx2.2), and pancreas and duodenum homeobox protein 1 (PDX-1) transcription factors have been shown to activate area IV-driven reporter gene expression as well as bind to this region of the endogenous gene in beta-cells. Analysis of the histone H3 and H4 acetylation level also indicated that areas I-IV are within transcriptionally active chromatin in beta-cells. Our data suggests that pdx-1 transcription is also regulated by factors acting upon conserved area IV sequences.
Gerrish
Kevin
K
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, Tennessee 37215, USA.
Van Velkinburgh
Jennifer C
JC
Stein
Roland
R
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002645:Chickens / Q000235:genetics; D002843:Chromatin; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051542:Hepatocyte Nuclear Factor 3-beta; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D029961:Zebrafish Proteins
D002843:Chromatin; D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; C496503:Foxa2 protein, mouse; C496504:Foxa2 protein, rat; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; C000715627:Nkx2-2 protein, mouse; C000715628:Nkx2-2 protein, rat; D009687:Nuclear Proteins; D009707:Nucleosomes; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish; C084010:pancreatic and duodenal homeobox 1 protein; D051542:Hepatocyte Nuclear Factor 3-beta