GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo.
We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental lactogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lactogen I and proliferin mRNAs to a level 50% below that reached in the wild-type placenta. Mutation of the GATA-2 gene had a similar effect on placental lactogen I expression, but led to a markedly greater reduction (5- to 6-fold) in proliferin gene expression. Placentas lacking GATA-2 secrete significantly less angiogenic activity than wild-type placentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin. Furthermore, within the same uterus the decidual tissue adjacent to mutant placentas displays markedly reduced neovascularization compared to the decidual tissue next to wild-type placentas. These results indicate that GATA-2 and GATA-3 are important in vivo regulators of trophoblast-specific gene expression and placental function, and reveal a difference in the effect of these two factors in regulating the synthesis of related placental hormones.
Ma
G T
GT
Department of Biochemistry, Northwestern University, Evanston, Illinois 60208, USA.
Roth
M E
ME
Groskopf
J C
JC
Tsai
F Y
FY
Orkin
S H
SH
Grosveld
F
F
Engel
J D
JD
Linzer
D I
DI
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D010928:Placental Lactogen / Q000235:genetics*; D011388:Prolactin; D011401:Promoter Regions, Genetic / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics; D014327:Trophoblasts / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000634106:Prl2c2 protein, mouse; D016372:RNA, Antisense; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D011388:Prolactin; D010928:Placental Lactogen