ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488265/SRR488265.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488270/SRR488270.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488267/SRR488267.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488266/SRR488266.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488268/SRR488268.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR488/SRR488269/SRR488269.fastq.gzprimary200OKGenomicsKUMChttps://www.ebi.ac.uk/ena/browser/view/PRJNA159725Mus musculusIn the preimplantation mouse embryo TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed both in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP-seq to define genome-wide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation towards the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification. Overall design: ChIPseq profiles of TEAD4, IgG, Input in Mouse trophoblast stem cells using Illumina HiSeq 2000 and Illumina Genome Analyzer IIxxref:PubMed:22529382ENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisestablishment and maintenance of substance location, RNA polymerase II core promoter proximal region sequence-specific binding, T-cell leukemia, RTEF1, EFTR-2, hRTEF-1B, AGL4, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, SEPALLATA 2, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Transcription Factor, TEF-3, Cell, transcription factor activity, single organism localization, TEFR-1, zinc ion regulated core promoter proximal region sequence-specific DNA binding, Lineage, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, establishment and maintenance of position, RNA polymerase II transcription factor activity, establishment and maintenance of localization, establishment and maintenance of substrate location, Etfr2, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, Rtef1, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, TEAD-4, Tefr, KNOTTED1-like homeobox gene 5, Tefr1a, F14P3.4, Transcription, Factors, FR-19, Lineages, F14P3_4, F10N7_150, single-organism localization, metal ion regulated core promoter proximal region sequence-specific binding, copper ion regulated core promoter proximal region sequence-specific binding, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription factor, F10N7.150, ETFR-2, localisation, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, TCF13L1, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, AGAMOUS-like 4, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, Tcf13r1, TEF3, Tef3, metal ion regulated sequence-specific DNA binding, Tefr1, Cell Lineages., metal ion regulated proximal promoter sequence-specific DNA binding, TRANSCRIPTION FACTOR, establishment and maintenance of cellular component location, RNA polymerase II distal enhancer sequence-specific bindingfalseMus musculusAltered Subcellular Localization of Transcription Factor TEAD4 Regulates First Mammalian Cell Lineage Commitment2025-09-242013-05-31PRJNA159725GSE373501009022529382