Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

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 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. ChIPseq profiles of TEAD4, IgG, Input in Mouse trophoblast stem cells using Illumina HiSeq 2000 and Illumina Genome Analyzer IIx

ORGANISM(S): Mus musculus

SUBMITTER: Byunggil Yoo

PROVIDER: E-GEOD-37350 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment.

Home Pratik P Saha Biswarup B Ray Soma S Dutta Debasree D Gunewardena Sumedha S Yoo Byunggil B Pal Arindam A Vivian Jay L JL Larson Melissa M Petroff Margaret M Gallagher Patrick G PG Schulz Vincent P VP White Kenneth L KL Golos Thaddeus G TG Behr Barry B Paul Soumen S

Proceedings of the National Academy of Sciences of the United States of America 20120423 19

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 ...[more]

PMID: 22529382

Similar Datasets

Project description:Aneuploidy has been well documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening (PGS) in a 24-hour protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy, and distinguishes certain meiotic from mitotic errors. In this study our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from seventeen couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e., one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of fifty-one (96.1%) inner cell mass (ICM) samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that trophectoderm karyotype is an excellent predictor of inner cell mass karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations. We thawed all fractions at 22°C, and then added Arcturus PicoPure Lysis Buffer (Molecular Devices, Sunnyvale, CA) to each of the biopsies. The tubes were incubated at 56°C for one hour, and then heat inactivated at 95°C for 10 minutes. DNA from the lysed biospsies was amplified using a commercial kit (GE Healthcare, Waukesha, WI) for multiple displacement amplification (MDA). MDA reactions were incubated at 30°C for 2.5 hours and then heat-inactivated at 65°C for five minutes. The amplified samples were genotyped using Illumina (San Diego, CA, USA) Infinium II genotyping microarrays (CytoSNP-12 chips) using a modified 24-hour protocol, as described previously*. Previously, we developed a genotyping microarray molecular karyotyping technology that uses parental genetic data to increase accuracy and determine mechanism and source of aneuploidy*. The algorithm uses parental genotypes and the observed distribution of unprocessed single cell microarray channel intensities to diagnose whole-chromosome imbalances and structural chromosome aberrations*. Because parental genotypes are available, the algorithm readily identifies parental source of whole-chromosome imbalances and structural chromosome aberrations. Additionally, the algorithm uses parental information, high confidence disomic single cell measurements on children, and recombination probabilities (genome.ucsc.edu) to determine the phase of the parental chromosomes. The phased data is then used to determine whether certain trisomies and uniparental disomies were mitotic or meiotic in origin*. *Johnson DS, Gemelos G, Baner J, Ryan A, Cinnioglu C, Banjevic M, Ross R, Alper M, Barrett B, Frederick J, Potter D, Behr B, Rabinowitz M. (2010). Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-hour protocol. Human Reproduction January 24 [Epub ahead of print].

Dataset Information

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

Publications

Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure