Linked Life Data

18704925

Source:http://linkedlifedata.com/resource/pubmed/id/18704925

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-10-2
pubmed:abstractText
Loss of the nuclear hormone receptor hepatocyte nuclear factor 4alpha (HNF4alpha) in hepatocytes results in a complex pleiotropic phenotype that includes a block in hepatocyte differentiation and a severe disruption to liver function. Recent analyses have shown that hepatic gene expression is severely affected by the absence of HNF4alpha, with expression of 567 genes reduced by > or =2.5-fold (P < or = 0.05) in Hnf4alpha(-/-) fetal livers. Although many of these genes are direct targets, HNF4alpha has also been shown to regulate expression of other liver transcription factors, and this raises the possibility that the dependence on HNF4alpha for normal expression of some genes may be indirect. We postulated that the identification of transcription factors whose expression is regulated by HNF4alpha might reveal roles for HNF4alpha in controlling hepatic functions that were not previously appreciated. Here we identify cyclic adenosine monophosphate responsive element binding protein H (CrebH) as a transcription factor whose messenger RNA can be identified in both the embryonic mouse liver and adult mouse liver and whose expression is dependent on HNF4alpha. Analyses of genomic DNA revealed an HNF4alpha binding site upstream of the CrebH coding sequence that was occupied by HNF4alpha in fetal livers and facilitated transcriptional activation of a reporter gene in transient transfection analyses. Although CrebH is highly expressed during hepatogenesis, CrebH(-/-) mice were viable and healthy and displayed no overt defects in liver formation. However, upon treatment with tunicamycin, which induces an endoplasmic reticulum (ER)-stress response, CrebH(-/-) mice displayed reduced expression of acute phase response proteins. CONCLUSION: These data implicate HNF4alpha in having a role in controlling the acute phase response of the liver induced by ER stress by regulating expression of CrebH.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/DK042394, http://linkedlifedata.com/resource/pubmed/grant/DK55743, http://linkedlifedata.com/resource/pubmed/grant/DK66226, http://linkedlifedata.com/resource/pubmed/grant/F32 DK067808-01, http://linkedlifedata.com/resource/pubmed/grant/F32 DK067808-02, http://linkedlifedata.com/resource/pubmed/grant/F32 DK067808-03, http://linkedlifedata.com/resource/pubmed/grant/HL052173, http://linkedlifedata.com/resource/pubmed/grant/HL057346, http://linkedlifedata.com/resource/pubmed/grant/P01 HL057346-100006, http://linkedlifedata.com/resource/pubmed/grant/P01 HL057346-11A18575, http://linkedlifedata.com/resource/pubmed/grant/R01 DK055743-09, http://linkedlifedata.com/resource/pubmed/grant/R01 DK066226-05, http://linkedlifedata.com/resource/pubmed/grant/R01 HL052173-11, http://linkedlifedata.com/resource/pubmed/grant/R01 HL052173-12, http://linkedlifedata.com/resource/pubmed/grant/R37 DK042394-10, http://linkedlifedata.com/resource/pubmed/grant/R37 DK042394-11, http://linkedlifedata.com/resource/pubmed/grant/R37 DK042394-12
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-10691738, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-10835623, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-11158324, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-11353085, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-11857799, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-11981036, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-12065599, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-12808453, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-14988562, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-15618518, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-15680365, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-15800215, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-16184190, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-16469704, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-16618389, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-16714383, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-16912278, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-1748280, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-2065662, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-2279702, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-7873404, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-7958910, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-8052626, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-8622695, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-8650183, http://linkedlifedata.com/resource/pubmed/commentcorrection/18704925-9774514
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1242-50
pubmed:dateRevised
2011-5-2
pubmed:meshHeading
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