BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation
Abstract Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 im...
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| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409160 |
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| author | Li Sun Xiuling Fu Zhen Xiao Gang Ma Yibin Zhou Haoqing Hu Liyang Shi Dongwei Li Ralf Jauch Andrew Paul Hutchins |
| author_facet | Li Sun Xiuling Fu Zhen Xiao Gang Ma Yibin Zhou Haoqing Hu Liyang Shi Dongwei Li Ralf Jauch Andrew Paul Hutchins |
| author_sort | Li Sun |
| collection | DOAJ |
| description | Abstract Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive‐specific genes. When Brd8 expression is reduced, chromatin accessibility is unchanged at primed‐specific genes, but histone acetylation is reduced. Conversely, naive‐specific genes has reduced repressive chromatin marks and acquired accessible chromatin more rapidly during the cell type conversion. It is shown that this process requires active histone deacetylation to promote the conversion of primed to naive. This data supports a model for BRD8 reading histone acetylation to accurately localize the genome‐wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability and both enables and impairs stem cell differentiation. |
| format | Article |
| id | doaj-art-569e4970c06449638e83c50af5c1928c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-569e4970c06449638e83c50af5c1928c2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202409160BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone AcetylationLi Sun0Xiuling Fu1Zhen Xiao2Gang Ma3Yibin Zhou4Haoqing Hu5Liyang Shi6Dongwei Li7Ralf Jauch8Andrew Paul Hutchins9Department of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaSchool of Biomedical Sciences Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaKey Laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education Institutes The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou 510799 ChinaSchool of Biomedical Sciences Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR ChinaDepartment of Systems Biology Southern University of Science and Technology Shenzhen 518055 ChinaAbstract Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive‐specific genes. When Brd8 expression is reduced, chromatin accessibility is unchanged at primed‐specific genes, but histone acetylation is reduced. Conversely, naive‐specific genes has reduced repressive chromatin marks and acquired accessible chromatin more rapidly during the cell type conversion. It is shown that this process requires active histone deacetylation to promote the conversion of primed to naive. This data supports a model for BRD8 reading histone acetylation to accurately localize the genome‐wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability and both enables and impairs stem cell differentiation.https://doi.org/10.1002/advs.202409160chromatinepigeneticshistone acetylationpluripotent stem cells |
| spellingShingle | Li Sun Xiuling Fu Zhen Xiao Gang Ma Yibin Zhou Haoqing Hu Liyang Shi Dongwei Li Ralf Jauch Andrew Paul Hutchins BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation Advanced Science chromatin epigenetics histone acetylation pluripotent stem cells |
| title | BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation |
| title_full | BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation |
| title_fullStr | BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation |
| title_full_unstemmed | BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation |
| title_short | BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation |
| title_sort | brd8 guards the pluripotent state by sensing and maintaining histone acetylation |
| topic | chromatin epigenetics histone acetylation pluripotent stem cells |
| url | https://doi.org/10.1002/advs.202409160 |
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