| pubmed-article:11266553 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11266553 | lifeskim:mentions | umls-concept:C1552603 | lld:lifeskim |
| pubmed-article:11266553 | lifeskim:mentions | umls-concept:C1706202 | lld:lifeskim |
| pubmed-article:11266553 | lifeskim:mentions | umls-concept:C1332838 | lld:lifeskim |
| pubmed-article:11266553 | lifeskim:mentions | umls-concept:C0215249 | lld:lifeskim |
| pubmed-article:11266553 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:11266553 | pubmed:dateCreated | 2001-3-27 | lld:pubmed |
| pubmed-article:11266553 | pubmed:abstractText | Activation of genes by heavy metals, notably zinc, cadmium and copper, depends on MTF-1, a unique zinc finger transcription factor conserved from insects to human. Knockout of MTF-1 in the mouse results in embryonic lethality due to liver decay, while knockout of its best characterized target genes, the stress-inducible metallothionein genes I and II, is viable, suggesting additional target genes of MTF-1. Here we report on a multi-pronged search for potential target genes of MTF-1, including microarray screening, SABRE selective amplification, a computer search for MREs (DNA-binding sites of MTF-1) and transfection of reporter genes driven by candidate gene promoters. Some new candidate target genes emerged, including those encoding alpha-fetoprotein, the liver-enriched transcription factor C/EBPalpha and tear lipocalin/von Ebner's gland protein, all of which have a role in toxicity/the cell stress response. In contrast, expression of other cell stress-associated genes, such as those for superoxide dismutases, thioredoxin and heat shock proteins, do not appear to be affected by loss of MTF-1. Our experiments have also exposed some problems with target gene searches. First, finding the optimal time window for detecting MTF-1 target genes in a lethal phenotype of rapid liver decay proved problematical: 12.5-day-old mouse embryos (stage E12.5) yielded hardly any differentially expressed genes, whereas at stage 13.0 reduced expression of secretory liver proteins probably reflected the onset of liver decay, i.e. a secondary effect. Likewise, up-regulation of some proliferation-associated genes may also just reflect responses to the concomitant loss of hepatocytes. Another sobering finding concerns gamma-glutamylcysteine synthetase(hc) (gamma-GCS(hc)), which controls synthesis of the antioxidant glutathione and which was previously suggested to be a target gene contributing to the lethal phenotype in MTF-1 knockout mice. gamma-GCS(hc) mRNA is reduced at the onset of liver decay but MTF-1 null mutant embryos manage to maintain a very high glutathione level until shortly before that stage, perhaps in an attempt to compensate for low expression of metallothioneins, which also have a role as antioxidants. | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11266553 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11266553 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11266553 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:11266553 | pubmed:issn | 1362-4962 | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:SchaffnerWW | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:LichtlenPP | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:WangYY | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:SackRR | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:Cern?MM | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:GeorgievOO | lld:pubmed |
| pubmed-article:11266553 | pubmed:author | pubmed-author:BelserTT | lld:pubmed |
| pubmed-article:11266553 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:11266553 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:11266553 | pubmed:volume | 29 | lld:pubmed |
| pubmed-article:11266553 | pubmed:owner | NLM | lld:pubmed |
