title: GATA3 inhibits GCM1 activity and trophoblast cell invasion.
abstract: Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular factors. Here we show that GATA3 interacts with GCM1 and inhibits its activity to suppress trophoblastic invasion. Immunohistochemistry demonstrates that GATA3 and GCM1 are coexpressed in villous cytotrophoblast cells, syncytiotrophoblast layer, and extravillous trophoblast cells of human placenta. Interestingly, GATA3 interacts with GCM1, but not the GCM2 homologue, through the DNA-binding domain and first transcriptional activation domain in GCM1 and the transcriptional activation domains and zinc finger 1 domain in GATA3. While GATA3 did not affect DNA-binding activity of GCM1, it suppressed transcriptional activity of GCM1 and therefore HtrA4 promoter activity. Correspondingly, GATA3 knockdown elevated HtrA4 expression in BeWo and JEG-3 trophoblast cell lines and enhanced the invasion activities of both lines. This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion.
authors.affiliation: Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.|Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Yueh Ho
authors.initials: YH
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.|Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Hungwen
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D057057:Serine Proteases / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C491089:GCM1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; C576189:HtrA4 protein, human; D057057:Serine Proteases