Next Generation Sequencing of Ad-Ctrl sh and Ad-Tox4 sh treated mouse livers
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE184239 | GEO | 2022/01/01
REPOSITORIES: GEO
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Project description:Next Generation Sequencing of Ad-Ctrl sh and Ad-Tox4 sh treated mouse livers
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Project description:Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate, using reprogramming efficiency towards iPSCs as an assay. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.
2019-09-19 | GSE127930 | GEO
Project description:Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate, using reprogramming efficiency towards iPSCs as an assay. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.
2019-09-19 | GSE127932 | GEO
Project description:HMG-box protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that although pan-hematopoietic Tox4 knockout produces minimal defects, T cell-specific knockout reduces thymic cellularity by 50% and increases cell death. In addition, single cell RNA-seq discovered that Tox4 loss impairs T cell development starting from double positive (DP) blast stage partially due to downregulation of genes critical for cell cycle progression through G2 and M phases. Moreover, Tox4 loss decreases transcriptional output of thousands of genes in DP cells, and mechanistically, Tox4 restricts transcriptional elongation and facilitates transcriptional reinitiation in a dephosphorylation-dependent manner, which is consistent with what we have found in human cells. Furthermore, small effect of Tox4 loss on chromatin accessibility suggest that it mainly regulates transcription in an HMG box independent manner. These results establish an evolutionarily conserved a role of Tox4 in transcriptional elongation and reinitiation.
2023-09-08 | GSE190039 | GEO
Project description:HMG-box protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that although pan-hematopoietic Tox4 knockout produces minimal defects, T cell-specific knockout reduces thymic cellularity by 50% and increases cell death. In addition, single cell RNA-seq discovered that Tox4 loss impairs T cell development starting from double positive (DP) blast stage partially due to downregulation of genes critical for cell cycle progression through G2 and M phases. Moreover, Tox4 loss decreases transcriptional output of thousands of genes in DP cells, and mechanistically, Tox4 restricts transcriptional elongation and facilitates transcriptional reinitiation in a dephosphorylation-dependent manner, which is consistent with what we have found in human cells. Furthermore, small effect of Tox4 loss on chromatin accessibility suggest that it mainly regulates transcription in an HMG box independent manner. These results establish an evolutionarily conserved a role of Tox4 in transcriptional elongation and reinitiation.
2023-09-08 | GSE190038 | GEO
Project description:HMG-box protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that although pan-hematopoietic Tox4 knockout produces minimal defects, T cell-specific knockout reduces thymic cellularity by 50% and increases cell death. In addition, single cell RNA-seq discovered that Tox4 loss impairs T cell development starting from double positive (DP) blast stage partially due to downregulation of genes critical for cell cycle progression through G2 and M phases. Moreover, Tox4 loss decreases transcriptional output of thousands of genes in DP cells, and mechanistically, Tox4 restricts transcriptional elongation and facilitates transcriptional reinitiation in a dephosphorylation-dependent manner, which is consistent with what we have found in human cells. Furthermore, small effect of Tox4 loss on chromatin accessibility suggest that it mainly regulates transcription in an HMG box independent manner. These results establish an evolutionarily conserved a role of Tox4 in transcriptional elongation and reinitiation.
2023-09-08 | GSE192698 | GEO
Project description:HMG-box protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that although pan-hematopoietic Tox4 knockout produces minimal defects, T cell-specific knockout reduces thymic cellularity by 50% and increases cell death. In addition, single cell RNA-seq discovered that Tox4 loss impairs T cell development starting from double positive (DP) blast stage partially due to downregulation of genes critical for cell cycle progression through G2 and M phases. Moreover, Tox4 loss decreases transcriptional output of thousands of genes in DP cells, and mechanistically, Tox4 restricts transcriptional elongation and facilitates transcriptional reinitiation in a dephosphorylation-dependent manner, which is consistent with what we have found in human cells. Furthermore, small effect of Tox4 loss on chromatin accessibility suggest that it mainly regulates transcription in an HMG box independent manner. These results establish an evolutionarily conserved a role of Tox4 in transcriptional elongation and reinitiation.
2023-09-08 | GSE190217 | GEO
Project description:HMG-box protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that although pan-hematopoietic Tox4 knockout produces minimal defects, T cell-specific knockout reduces thymic cellularity by 50% and increases cell death. In addition, single cell RNA-seq discovered that Tox4 loss impairs T cell development starting from double positive (DP) blast stage partially due to downregulation of genes critical for cell cycle progression through G2 and M phases. Moreover, Tox4 loss decreases transcriptional output of thousands of genes in DP cells, and mechanistically, Tox4 restricts transcriptional elongation and facilitates transcriptional reinitiation in a dephosphorylation-dependent manner, which is consistent with what we have found in human cells. Furthermore, small effect of Tox4 loss on chromatin accessibility suggest that it mainly regulates transcription in an HMG box independent manner. These results establish an evolutionarily conserved a role of Tox4 in transcriptional elongation and reinitiation.
2023-09-08 | GSE190040 | GEO
Project description:TOX4 is one of the regulatory proteins of PP1 phosphatases with poorly understood functions. Here we show that chromatin occupancy pattern of TOX4 resembles that of RNA polymerase II (Pol II), and its loss increases cellular level of C-terminal domain (CTD) phosphorylated Pol II but mainly decreases Pol II occupancy on promoters. In addition, elongation rate analyses by 4sUDRB-seq suggest that TOX4 restricts pause release and early elongation but promotes late elongation. Moreover, TT-seq analyses indicate that TOX4 loss mainly decreases transcriptional output. Mechanistically, TOX4 may restrict pause release through facilitating CTD serine 2 and DSIF dephosphorylation, and promote Pol II recycling and reinitiation through facilitating CTD serines 2 and 5 dephosphorylation. Furthermore, among the PP1 phosphatases, TOX4 preferentially binds PP1α and is capable of facilitating Pol II CTD dephosphorylation in vitro. These results lay the foundation for a better understanding of the role of TOX4 in transcriptional regulation.
2022-03-29 | GSE164277 | GEO
Project description:Tox4 Modulates Cell Fate Reprogramming
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