title: GATA3 is selectively expressed in the trophectoderm of peri-implantation embryo and directly regulates Cdx2 gene expression.
abstract: During early mammalian development, genesis of the first two cell lineages, inner cell mass (ICM) and trophectoderm (TE), is dependent upon functions of key transcription factors that are expressed in a regulated and spatially restricted fashion. In this study, we demonstrate that during early mouse development, mRNA expression of transcription factor GATA3 is induced at the 4-cell stage and is consistently present during pre-implantation embryonic development. Interestingly, at the blastocyst stage, Gata3 mRNA is selectively up-regulated within the TE lineage, and GATA3 protein is abundantly present only in the TE but not in the ICM. Using mouse trophoblast stem cells (TS cells) as a model, we found that, knockdown of GATA3 by RNA interference (RNAi) down-regulates expression of caudal-type homeobox 2 (CDX2), a key regulator of the TE lineage. Chromatin immunoprecipitation (ChIP) analyses revealed that, in TS cells, GATA3 directly regulates Cdx2 transcription from a conserved GATA motif at the intron 1 region of the Cdx2 locus. ChIP analyses with mouse blastocysts also detected GATA3 occupancy at intron 1 of the Cdx2 locus. In addition, down-regulation of GATA3 in pre-implantation mouse embryos reduces Cdx2 expression and inhibits morula to blastocyst transformation. Our results indicate a novel function of GATA3, in which it is selectively expressed in TE, regulates expression of key genes in TE lineage, and is involved in morula to blastocyst transformation.
authors.affiliation: Institute of Maternal-Fetal Biology, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Home
authors.forename: Soma
authors.initials: S
authors.lastname: Ray
authors.forename: Debasree
authors.initials: D
authors.lastname: Dutta
authors.forename: Illya
authors.initials: I
authors.lastname: Bronshteyn
authors.forename: Melissa
authors.initials: M
authors.lastname: Larson
authors.forename: Soumen
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D018929:Cell Culture Techniques; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D004475:Ectoderm / Q000378:metabolism*; D010064:Embryo Implantation / Q000235:genetics*; D050990:GATA3 Transcription Factor / Q000096:biosynthesis* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors
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