Transcription factor GATA-6 activates expression of gastroprotective trefoil genes TFF1 and TFF2.
One of the early events in inflammation and epithelial restitution of the gastrointestinal tract is the up-regulation of secretory peptides belonging to the trefoil factor family (TFF) that promote cell migration, protect and heal the mucosa. Their major expression site is stomach (TFF1, TFF2) and intestine (TFF3). Located in the 5'-flanking region of the genes are several consensus sites for members of the GATA transcription factors known to control gut-specific gene expression. By reverse transcription-PCR (RT-PCR), GATA-6 was shown to be expressed in a variety of tumor cell lines of gastric, intestinal and pancreatic origin. In MKN45, KATOIII and LS174T, cotransfection with TFF reporter genes and GATA-6 expression vectors revealed that GATA-6 activates TFF1 and TFF2 4-6-fold, without an effect on TFF3. The functional contribution of GATA binding sequences in the reverse orientation was further characterized by reporter gene assays using TFF2 deletion constructs and by gel shift experiments.
Al-azzeh
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ED
Division of Molecular Genetics, Institute of Anthropology and Human Genetics, University of Tübingen, Wilhelmstrasse 27, D-72074, Tübingen, Germany.
Fegert
P
P
Blin
N
N
Gött
P
P
D000230:Adenocarcinoma; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050993:GATA6 Transcription Factor; D017930:Genes, Reporter; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D014157:Transcription Factors; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins