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Gata3 acts alongside Cdx2 to promote trophoblast gene expression downstream of Tead4 during mouse development

ABSTRACT: The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE12999 | GEO | 2010/02/01

SECONDARY ACCESSION(S): PRJNA112611

REPOSITORIES: GEO

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Gata3 acts alongside Cdx2 to promote trophoblast gene expression downstream of Tead4 during mouse development

Project description:The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage. This SuperSeries is composed of the following subset Series: GSE12985: Differentiation time course of trophoblast stem cells GSE12986: Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

2010-02-21 | E-GEOD-12999 | biostudies-arrayexpress

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Altered Subcellular Localization of Transcription Factor TEAD4 Regulates First Mammalian Cell Lineage Commitment

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Project description:Although Tead4 is well-known to be critical for blastocyst development and trophoblast lineage differentiation, the higher-order chromatin organization around this gene remains poorly understood. We assayed long-range chromosomal interactions on the Tead4 promoter in mouse embryonic stem (ES) cells and trophoblast stem (TS) cells using the circular chromosome conformation capture (4C)-seq technique. We observed frequent overlaps of genomic regions interacting with the Tead4 promoter and open chromatin regions identified by FAIRE-seq in TS cells. By systematic reporter assays using ES and TS cells, we identified five genomic fragments possessing a TS-specific enhancer activity to the Tead4 promoter, consisting of two intra- and three inter-chromosomal loci relative to the Tead4 gene on chromosome 6. We established five mouse lines deleted with one of the five enhancer elements using CRISPR/Cas9 genome editing, and evaluated the effect of each of the enhancer deletions on the Tead4 gene expression at the blastocyst stage. We observed 35-50% decrease of the Tead4 expression in the blastocysts with heterozygous or homozygous deletion of an inter-chromosomally located enhancer on chromosome 19 compared to that in wild-type blastocysts, whereas the other four deletions did not affect the Tead4 expression level. Our results demonstrate that inter-chromosomal enhancer-promoter interaction bears a critical role in assuring the appropriate level of Tead4 gene expression at the trophoblast lineage specification.

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Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

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Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

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