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Tox4 regulates transcriptional elongation and reinitiation during murine T cell development
HMG protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that Tox4 conditional knockout in mice reduces thymic cellularity, partially blocks T cell development, and decreases ratio of CD8 to CD4 through decreasing proliferation and increasing apoptosis o...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247741/ https://www.ncbi.nlm.nih.gov/pubmed/37286708 http://dx.doi.org/10.1038/s42003-023-04992-y |
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author | Wang, Talang Zhao, Ruoyu Zhi, Junhong Liu, Ziling Wu, Aiwei Yang, Zimei Wang, Weixu Ni, Ting Jing, Lili Yu, Ming |
author_facet | Wang, Talang Zhao, Ruoyu Zhi, Junhong Liu, Ziling Wu, Aiwei Yang, Zimei Wang, Weixu Ni, Ting Jing, Lili Yu, Ming |
author_sort | Wang, Talang |
collection | PubMed |
description | HMG protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that Tox4 conditional knockout in mice reduces thymic cellularity, partially blocks T cell development, and decreases ratio of CD8 to CD4 through decreasing proliferation and increasing apoptosis of CD8 cells. In addition, single-cell RNA-seq discovered that Tox4 loss also impairs proliferation of the fast-proliferating double positive (DP) blast population within DP cells in part due to downregulation of genes critical for proliferation, notably Cdk1. Moreover, genes with high and low expression level are more dependent on Tox4 than genes with medium expression level. Mechanistically, Tox4 may facilitate transcriptional reinitiation and restrict elongation in a dephosphorylation-dependent manner, a mechanism that is conserved between mouse and human. These results provide insights into the role of TOX4 in development and establish it as an evolutionarily conserved regulator of transcriptional elongation and reinitiation. |
format | Online Article Text |
id | pubmed-10247741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102477412023-06-09 Tox4 regulates transcriptional elongation and reinitiation during murine T cell development Wang, Talang Zhao, Ruoyu Zhi, Junhong Liu, Ziling Wu, Aiwei Yang, Zimei Wang, Weixu Ni, Ting Jing, Lili Yu, Ming Commun Biol Article HMG protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that Tox4 conditional knockout in mice reduces thymic cellularity, partially blocks T cell development, and decreases ratio of CD8 to CD4 through decreasing proliferation and increasing apoptosis of CD8 cells. In addition, single-cell RNA-seq discovered that Tox4 loss also impairs proliferation of the fast-proliferating double positive (DP) blast population within DP cells in part due to downregulation of genes critical for proliferation, notably Cdk1. Moreover, genes with high and low expression level are more dependent on Tox4 than genes with medium expression level. Mechanistically, Tox4 may facilitate transcriptional reinitiation and restrict elongation in a dephosphorylation-dependent manner, a mechanism that is conserved between mouse and human. These results provide insights into the role of TOX4 in development and establish it as an evolutionarily conserved regulator of transcriptional elongation and reinitiation. Nature Publishing Group UK 2023-06-07 /pmc/articles/PMC10247741/ /pubmed/37286708 http://dx.doi.org/10.1038/s42003-023-04992-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Talang Zhao, Ruoyu Zhi, Junhong Liu, Ziling Wu, Aiwei Yang, Zimei Wang, Weixu Ni, Ting Jing, Lili Yu, Ming Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title | Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title_full | Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title_fullStr | Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title_full_unstemmed | Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title_short | Tox4 regulates transcriptional elongation and reinitiation during murine T cell development |
title_sort | tox4 regulates transcriptional elongation and reinitiation during murine t cell development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247741/ https://www.ncbi.nlm.nih.gov/pubmed/37286708 http://dx.doi.org/10.1038/s42003-023-04992-y |
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