| pubmed-article:17290224 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17290224 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:17290224 | lifeskim:mentions | umls-concept:C1514562 | lld:lifeskim |
| pubmed-article:17290224 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:17290224 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:17290224 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:17290224 | pubmed:dateCreated | 2007-2-21 | lld:pubmed |
| pubmed-article:17290224 | pubmed:abstractText | The C/EBPalpha transcription factor regulates hepatic nitrogen, glucose, lipid and iron metabolism. However, how it is able to independently control these processes is not known. Here, we use mouse knock-in mutagenesis to identify C/EBPalpha domains that specifically regulate hepatic gluconeogenesis and lipogenesis. In vivo deletion of a proline-histidine rich domain (PHR), dephosphorylated at S193 by insulin signaling, dysregulated genes involved in the generation of acetyl-CoA and NADPH for triglyceride synthesis and led to increased hepatic lipogenesis. These promoters bound SREBP-1 as well as C/EBPalpha, and the PHR was required for C/EBPalpha-SREBP transcriptional synergy. In contrast, the highly conserved C/EBPalpha CR4 domain was found to undergo liver-specific dephosphorylation of residues T222 and T226 upon fasting, and alanine mutation of these residues upregulated the hepatic expression of the gluconeogenic G6Pase and PEPCK mRNAs, but not PGC-1alpha, leading to glucose intolerance. Our results show that pathway-specific metabolic regulation can be achieved through a single transcription factor containing context-sensitive regulatory domains, and indicate C/EBPalpha phosphorylation as a PGC-1alpha-independent mechanism for regulating hepatic gluconeogenesis. | lld:pubmed |
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| pubmed-article:17290224 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:17290224 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17290224 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17290224 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:17290224 | pubmed:issn | 0261-4189 | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:MandrupSusann... | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:NerlovClausC | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:ErmakovaOlgaO | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:BereshchenkoO... | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:Garcia-SilvaS... | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:PorseBo TBT | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:KurzElkeE | lld:pubmed |
| pubmed-article:17290224 | pubmed:author | pubmed-author:PedersenThoma... | lld:pubmed |
| pubmed-article:17290224 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17290224 | pubmed:day | 21 | lld:pubmed |
| pubmed-article:17290224 | pubmed:volume | 26 | lld:pubmed |
| pubmed-article:17290224 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17290224 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17290224 | pubmed:pagination | 1081-93 | lld:pubmed |
| pubmed-article:17290224 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:17290224 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17290224 | pubmed:articleTitle | Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene expression in vivo. | lld:pubmed |
| pubmed-article:17290224 | pubmed:affiliation | EMBL Mouse Biology Unit, Monterotondo, Italy. | lld:pubmed |
| pubmed-article:17290224 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17290224 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:17290224 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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