Similar Datasets
Project description:Smad7 has been identified as a negative regulator of the transforming growth factor TGF-β pathway by direct interaction with the TGF-β type I receptor (TβR-I). Although Smad7 has also been shown to play TGF-β unrelated functions in the cytoplasm and in the nucleus, a comprehensive analysis of its nuclear function has not yet been performed. Here, we show that in ESCs Smad7 is mainly nuclear and acts as a general transcription factor regulating several genes unrelated to the TGF-β pathway. Loss of Smad7 results in the downregulation of several key stemness master regulators, including Pou5f1 and Zfp42, and in the upregulation of developmental genes, with consequent loss of the stem phenotype. Integrative analysis of genome-wide mapping data for Smad7 and ESC self-renewal and pluripotency transcriptional regulators revealed that Smad7 co-occupies promoters of highly expressed key stemness regulators genes, by binding to a specific consensus response element NCGGAAMM. Altogether, our data establishes Smad7 as a new, integral component of the regulatory circuitry that controls ESC identity.
| S-EPMC8708723 | biostudies-literature
Project description:Smad7 has been identified as a negative regulator of the transforming growth factor TGF-β pathway by direct interaction with the TGF-β type I receptor (TβR-I). Although Smad7 has also been shown to play TGF-β unrelated functions in the cytoplasm and in the nucleus, a comprehensive analysis of its nuclear function has not yet been performed. Here we show that in ESCs Smad7 is mainly nuclear and acts as a general transcription factor regulating a number of genes unrelated to the TGF-β pathway. Loss of Smad7 results in the downregulation of several key stemness master regulators, including Pou5f1 and Zfp42, and in the upregulation of developmental genes, with consequent loss of the stem phenotype. Integrative analysis of genome-wide mapping data for Smad7 and ESC self-renewal and pluripotency transcriptional regulators revealed that Smad7 co-occupies promoters of highly expressed key stemness regulators genes, by binding to a specific consensus response element NCGGAAMM. Altogether, our data establishes Smad7 as new integral component of the regulatory circuitry that controls ESC identity.
2022-01-05 | GSE185904 | GEO
Project description:Smad7 has been identified as a negative regulator of the transforming growth factor TGF-β pathway by direct interaction with the TGF-β type I receptor (TβR-I). Although Smad7 has also been shown to play TGF-β unrelated functions in the cytoplasm and in the nucleus, a comprehensive analysis of its nuclear function has not yet been performed. Here we show that in ESCs Smad7 is mainly nuclear and acts as a general transcription factor regulating a number of genes unrelated to the TGF-β pathway. Loss of Smad7 results in the downregulation of several key stemness master regulators, including Pou5f1 and Zfp42, and in the upregulation of developmental genes, with consequent loss of the stem phenotype. Integrative analysis of genome-wide mapping data for Smad7 and ESC self-renewal and pluripotency transcriptional regulators revealed that Smad7 co-occupies promoters of highly expressed key stemness regulators genes, by binding to a specific consensus response element NCGGAAMM. Altogether, our data establishes Smad7 as new integral component of the regulatory circuitry that controls ESC identity.
2022-01-05 | GSE185902 | GEO
Project description:Genome-wide Analysis of Smad7-Mediated Transcription in Mouse Embryonic Stem Cells
| PRJNA771271 | ENA
Project description:Genome-wide Analysis of Smad7-Mediated Transcription in Mouse Embryonic Stem Cells [RNA-Seq]
| PRJNA771275 | ENA
Project description:Genome-wide Analysis of Smad7-Mediated Transcription in Mouse Embryonic Stem Cells [ChIP-Seq]
| PRJNA771268 | ENA
Project description:Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, the mechanism underlying the regulation of transcriptional bursting kinetics (burst size and frequency) in mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing to analyze the intrinsic noise and mRNA levels for elucidating the transcriptional bursting kinetics in mouse embryonic stem cells. Informatics analyses and functional assays revealed that transcriptional bursting kinetics was regulated by a combination of promoter- and gene body-binding proteins, including the polycomb repressive complex 2 and transcription elongation factors. Furthermore, large-scale CRISPR-Cas9-based screening identified that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncovered the key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.
| S-EPMC7299619 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-06-04 | GSE132593 | GEO
Project description:Inner cell mass (ICM) cells of a blastocyst, the source of embryonic stem (ES) cells, are characterized by their unique ability to give rise to all cell types in adult organisms. The epigenomes of germ cells and developing zygotes undergo extensive reprogramming to acquire such a pluripotent state. A major reprogramming event during early embryonic development is the erasure and subsequent re-establishment of patterns of methylation at the 5-position of cytosine (5mC). The recent demonstration that Ten-eleven translocation family proteins, Tet1-3 have the capacity to convert 5mC to 5-hydroxymethylcytosine (5hmC) raises the possibility that 5hmC may act as an distinct epigenetic state contributing to dynamic changes in DNA methylation and transcriptional regulation during embryonic development. In ES cells, Tet1 is highly expressed and 5hmC is present at relatively high levels compared to most differentiated cells, but the functional significance of Tet1 and 5hmC in these pluripotent cells are not clear. Recently, a flurry of papers that profile the distribution of Tet1 and/or 5hmC across the genome of mouse ES cells provide new insights into the role of Tet proteins and 5hmC in regulating expression of genes related to pluripotency and cellular differentiation. Through integrative analyses of datasets from different groups, we reveal the common Tet1 and 5hmC targets in undifferentiated mouse ES cells, which suggest that Tet1 may play a key role in orchestrating the balance between pluripotent and lineage committed states.
| S-EPMC3180185 | biostudies-literature
Project description:Direct reprogramming can be achieved by forced expression of master transcription factors. Yet how such factors mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Through embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS cell-specific 'CAG' factors (Cdx2, Arid3a and Gata3), we interrogate their chromosomal target occupancies, modulation of global transcription and chromatin accessibility at the initial stage of reprogramming. From the studies, we uncover a sequential, two-step mechanism of cellular reprogramming in which repression of pre-existing ES cell-associated gene expression program is followed by activation of TS cell-specific genes by CAG factors. Therefore, we reveal that CAG factors function as both decommission and pioneer factors during ES to TS-like cell fate conversion.
| S-EPMC5737334 | biostudies-literature