title: Transcription factor AP-2γ is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis.
abstract: The trophectoderm epithelium is the first differentiated cell layer to arise during mammalian development. Blastocyst formation requires the proper expression and localization of tight junction, polarity, ion gradient and H2O channel proteins in the outer cell membranes. However, the underlying transcriptional mechanisms that control their expression are largely unknown. Here, we report that transcription factor AP-2γ (Tcfap2c) is a core regulator of blastocyst formation in mice. Bioinformatics, chromatin immunoprecipitation and transcriptional analysis revealed that Tcfap2c binds and regulates a diverse group of genes expressed during blastocyst formation. RNA interference experiments demonstrated that Tcfap2c regulates genes important for tight junctions, cell polarity and fluid accumulation. Functional and ultrastructural studies revealed that Tcfap2c is necessary for tight junction assembly and paracellular sealing in trophectoderm epithelium. Aggregation of control eight-cell embryos with Tcfap2c knockdown embryos rescued blastocyst formation via direct contribution to the trophectoderm epithelium. Finally, we found that Tcfap2c promotes cellular proliferation via direct repression of p21 transcription during the morula-to-blastocyst transition. We propose a model in which Tcfap2c acts in a hierarchy to facilitate blastocyst formation through transcriptional regulation of core genes involved in tight junction assembly, fluid accumulation and cellular proliferation.
authors.affiliation: Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI, USA.
authors.forename: Inchul
authors.initials: I
authors.lastname: Choi
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Carey
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wilson
authors.forename: Jason G
authors.initials: JG
authors.lastname: Knott
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007477:Ions; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D019108:Tight Junctions / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D007477:Ions; C583890:Tfap2c protein, mouse; D050656:Transcription Factor AP-2