Linked Life Data

16100117

Source:http://linkedlifedata.com/resource/pubmed/id/16100117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2005-10-3
pubmed:abstractText
The hepatic transcriptional regulation by glucocorticoids of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C) gene is coordinated by interactions of specific transcription factors at the glucocorticoid regulatory unit (GRU). We propose an extended GRU that consists of four accessory sites, two proximal AF1 and AF2 sites and their distal counterpart dAF1 (-993) and a new site, dAF2 (-1365); together, these four sites form a palindrome. Sequencing and gel shift binding assays of hepatic nuclear proteins interacting with these sites indicated similarity of dAF1 and dAF2 sites to the GRU proximal AF1 and AF2 sites. Chromatin immunoprecipitation assays demonstrated that glucocorticoids enhanced the binding of FOXO1 and peroxisome proliferator-activated receptor-alpha to AF2 and dAF2 sites and not to dAF1 site but enhanced the binding of hepatic nuclear transcription factor-4alpha only to the dAF1 site. Insulin inhibited the binding of these factors to their respective sites but intensified the binding of phosphorylated FOXO1. Transient transfections in HepG2 human hepatoma cells showed that glucocorticoid receptor interacts with several non-steroid nuclear receptors, yielding a synergistic response of the PEPCK-C gene promoter to glucocorticoids. The synergistic stimulation by glucocorticoid receptor together with peroxisome proliferator-activated receptor-alpha or hepatic nuclear transcription factor-4alpha requires all four accessory sites, i.e. a mutation of each of these markedly affects the synergistic response. Mice with a targeted mutation of the dAF1 site confirmed this requirement. This mutation inhibited the full response of hepatic PEPCK-C gene to diabetes by reducing PEPCK-C mRNA level by 3.5-fold and the level of circulating glucose by 25%.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33873-84
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16100117-Animals, pubmed-meshheading:16100117-Carcinoma, Hepatocellular, pubmed-meshheading:16100117-Chromatin, pubmed-meshheading:16100117-Forkhead Transcription Factors, pubmed-meshheading:16100117-Gene Expression Regulation, pubmed-meshheading:16100117-Glucocorticoids, pubmed-meshheading:16100117-Hypoglycemic Agents, pubmed-meshheading:16100117-Immunoprecipitation, pubmed-meshheading:16100117-Insulin, pubmed-meshheading:16100117-Liver, pubmed-meshheading:16100117-Liver Neoplasms, pubmed-meshheading:16100117-Mice, pubmed-meshheading:16100117-Mice, Transgenic, pubmed-meshheading:16100117-Mutagenesis, Site-Directed, pubmed-meshheading:16100117-PPAR alpha, pubmed-meshheading:16100117-Phosphoenolpyruvate Carboxykinase (GTP), pubmed-meshheading:16100117-Promoter Regions, Genetic, pubmed-meshheading:16100117-Receptors, Glucocorticoid, pubmed-meshheading:16100117-Transcription, Genetic, pubmed-meshheading:16100117-Transfection, pubmed-meshheading:16100117-Tumor Cells, Cultured
pubmed:year
2005
pubmed:articleTitle
Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate carboxykinase in the liver via an extended glucocorticoid regulatory unit.
pubmed:affiliation
Department of Developmental Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, 91120 Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural