Pancreatic-Duodenal Homeobox 1 Regulates Expression of Liver Receptor Homolog 1 during Pancreas Development
2003; Taylor & Francis; Volume: 23; Issue: 19 Linguagem: Inglês
10.1128/mcb.23.19.6713-6724.2003
ISSN1098-5549
AutoresJean‐Sébastien Annicotte, Elisabeth Fayard, Galvin H. Swift, Lars Selander, Helena Edlund, Toshiya Tanaka, Tatsuhiko Kodama, Kristina Schoonjans, Johan Auwerx,
Tópico(s)Genetics and Neurodevelopmental Disorders
ResumoLiver 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.
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