Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-9-18
pubmed:abstractText
Pancreatic and duodenal homeobox factor 1 (Pdx1) has been demonstrated to play a crucial role in pancreas development and in maintenance of mature beta-cell function. However, it remains to be elucidated how Pdx1 gene expression is regulated in non-beta cells during pancreas development. Pdx1 and Ptf1a are expressed in pancreatic progenitor cells, which give rise to all three types of pancreatic tissue. In addition, Ptf1a has been shown to bind the mammalian Suppressor of Hairless (RBP-J) within the PTF1 complex. Furthermore, loss-of-function approaches have revealed that all three factors are essential for early pancreas development. We therefore hypothesized that Ptf1a and RBP-J regulate expression of the Pdx1 gene in pancreatic precursors. Reporter gene analyses showed that Ptf1a transactivated Pdx1 promoter in pancreatic Panc-1 cells, which was enhanced by RBP-J. Deletion/mutation analyses of the Pdx1 promoter and electrophoretic gel-mobility shift assays identified the Ptf1a binding site in the well-conserved regulatory sequence domain, termed Area III, which was also confirmed by the chromatin immunoprecipitation assay. Furthermore, adenovirus-mediated overexpression of Ptf1a, together with RBP-J, markedly increased Pdx1 protein levels in pancreatic AR42J-B13 cells. Our data suggest a novel transcriptional network, where Ptf1a and RBP-J cooperatively regulate Pdx1 gene expression through binding to Area III.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
362
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
905-9
pubmed:dateRevised
2011-6-1
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Ptf1a and RBP-J cooperate in activating Pdx1 gene expression through binding to Area III.
pubmed:affiliation
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. miyatuka@medone.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't