Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver
Abstract Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes in the level of transcriptional regulation...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-09-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202211002 |
| _version_ | 1797286984971976704 |
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| author | Mihaela Bozukova Chrysa Nikopoulou Niklas Kleinenkuhnen Dora Grbavac Katrin Goetsch Peter Tessarz |
| author_facet | Mihaela Bozukova Chrysa Nikopoulou Niklas Kleinenkuhnen Dora Grbavac Katrin Goetsch Peter Tessarz |
| author_sort | Mihaela Bozukova |
| collection | DOAJ |
| description | Abstract Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes in the level of transcriptional regulation. Here, we used a multi‐omics approach and integrated ATAC‐, RNA‐ and NET‐seq to identify age‐related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility, and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase in transcriptional output. Instead, aging is accompanied by a decrease in promoter‐proximal pausing of RNA polymerase II (Pol II), while initiation of transcription is not decreased as assessed by RNA polymerase mapping using CUT&RUN. Based on the data reported, we propose that these age‐related changes in transcriptional regulation are due to a reduced stability of the pausing complex. |
| first_indexed | 2024-03-07T18:26:21Z |
| format | Article |
| id | doaj.art-c65102c402d24f72a3ba53873d6608ca |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T18:26:21Z |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-c65102c402d24f72a3ba53873d6608ca2024-03-02T07:02:33ZengSpringer NatureMolecular Systems Biology1744-42922022-09-01189n/an/a10.15252/msb.202211002Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liverMihaela Bozukova0Chrysa Nikopoulou1Niklas Kleinenkuhnen2Dora Grbavac3Katrin Goetsch4Peter Tessarz5Max Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyMax Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyMax Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyMax Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyMax Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyMax Planck Research Group ‘Chromatin and Ageing’ Max Planck Institute for Biology of Ageing Cologne GermanyAbstract Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes in the level of transcriptional regulation. Here, we used a multi‐omics approach and integrated ATAC‐, RNA‐ and NET‐seq to identify age‐related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility, and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase in transcriptional output. Instead, aging is accompanied by a decrease in promoter‐proximal pausing of RNA polymerase II (Pol II), while initiation of transcription is not decreased as assessed by RNA polymerase mapping using CUT&RUN. Based on the data reported, we propose that these age‐related changes in transcriptional regulation are due to a reduced stability of the pausing complex.https://doi.org/10.15252/msb.202211002agingchromatin architecturenascent transcriptionpromoter‐proximal pausing |
| spellingShingle | Mihaela Bozukova Chrysa Nikopoulou Niklas Kleinenkuhnen Dora Grbavac Katrin Goetsch Peter Tessarz Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver Molecular Systems Biology aging chromatin architecture nascent transcription promoter‐proximal pausing |
| title | Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| title_full | Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| title_fullStr | Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| title_full_unstemmed | Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| title_short | Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| title_sort | aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver |
| topic | aging chromatin architecture nascent transcription promoter‐proximal pausing |
| url | https://doi.org/10.15252/msb.202211002 |
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