Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development.
Liver receptor homolog 1 (LRH-1) and pancreatic-duodenal homeobox 1 (PDX-1) are coexpressed in the pancreas during mouse embryonic development. Analysis of the regulatory region of the human LRH-1 gene demonstrated the presence of three functional binding sites for PDX-1. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed that PDX-1 bound to the LRH-1 promoter, both in cultured cells in vitro and during pancreatic development in vivo. Retroviral expression of PDX-1 in pancreatic cells induced the transcription of LRH-1, whereas reduced PDX-1 levels by RNA interference attenuated its expression. Consistent with direct regulation of LRH-1 expression by PDX-1, PDX-1(-/-) mice expressed smaller amounts of LRH-1 mRNA in the embryonic pancreas. Taken together, our data indicate that PDX-1 controls LRH-1 expression and identify LRH-1 as a novel downstream target in the PDX-1 regulatory cascade governing pancreatic development, differentiation, and function.
Annicotte
Jean-Sébastien
JS
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP 67404, Illkirch, France.
Fayard
Elisabeth
E
Swift
Galvin H
GH
Selander
Lars
L
Edlund
Helena
H
Tanaka
Toshiya
T
Kodama
Tatsuhiko
T
Schoonjans
Kristina
K
Auwerx
Johan
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein