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PMID:22529382

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Citation

Home, P, Saha, B, Ray, S, Dutta, D, Gunewardena, S, Yoo, B, Pal, A, Vivian, JL, Larson, M, Petroff, M, Gallagher, PG, Schulz, VP, White, KL, Golos, TG, Behr, B and Paul, S (2012) Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment. Proc. Natl. Acad. Sci. U.S.A. 109:7362-7

Abstract

In 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 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 sequencing to define genomewide 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 toward 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.

Links

PubMed PMC3358889 Online version:10.1073/pnas.1201595109

Keywords

Animals; Blastocyst/cytology; Blastocyst/metabolism; Blastocyst Inner Cell Mass/cytology; Blastocyst Inner Cell Mass/metabolism; Blastomeres/cytology; Blastomeres/metabolism; Blotting, Western; Cattle; Cell Lineage; Cell Nucleus/metabolism; Cells, Cultured; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryonic Stem Cells/metabolism; GATA3 Transcription Factor/genetics; GATA3 Transcription Factor/metabolism; Gene Expression Regulation, Developmental; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; HEK293 Cells; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Macaca mulatta; Mice; Mice, Transgenic; Muscle Proteins/genetics; Muscle Proteins/metabolism; RNA Interference; Rats; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BMP4

acts_upstream_of_or_within

GO:0042306: regulation of protein import into nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GATA3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GATA3

located_in

GO:0005634: nucleus

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P23771

C

Seeded From UniProt

complete

MOUSE:CDX2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:YAP1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TEAD4

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TEAD4

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TEAD4

part_of

GO:0032993: protein-DNA complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TEAD4

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TEAD4

acts_upstream_of_or_within

GO:0045165: cell fate commitment

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GATA3

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMP4

involved_in

GO:0042306: regulation of protein import into nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0042306: regulation of protein import into nucleus

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P12644

P

Seeded From UniProt

complete

MOUSE:GATA3

part_of

GO:0005634: nucleus

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P23771

C

Seeded From UniProt

complete

Notes

See also

References

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