Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress
Summary: Cardiomyocyte (CM) nuclei are constantly exposed to mechanical stress, but how they maintain their nuclear shape remains unknown. In this study, we found that ventricular CM nuclei acquire characteristic prominent spatial organizations of heterochromatin (SOH), which are disrupted by high-l...
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013998 |
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| author | Keita Fujiwara Tadashi Inoue Aya Kimoto Jiang Zixian Keizo Tokuhiro Yoshiki Yasukochi Tomoya O. Akama Chen-Leng Cai Ichiro Shiojima Hiroshi Kimura Shige H. Yoshimura Tomoyuki Nakamura Maretoshi Hirai |
| author_facet | Keita Fujiwara Tadashi Inoue Aya Kimoto Jiang Zixian Keizo Tokuhiro Yoshiki Yasukochi Tomoya O. Akama Chen-Leng Cai Ichiro Shiojima Hiroshi Kimura Shige H. Yoshimura Tomoyuki Nakamura Maretoshi Hirai |
| author_sort | Keita Fujiwara |
| collection | DOAJ |
| description | Summary: Cardiomyocyte (CM) nuclei are constantly exposed to mechanical stress, but how they maintain their nuclear shape remains unknown. In this study, we found that ventricular CM nuclei acquire characteristic prominent spatial organizations of heterochromatin (SOH), which are disrupted by high-level expression of H2B-mCherry in mice. SOH disruption was associated with nuclear softening, leading to extreme elongation and rupture under unidirectional mechanical stress. Loosened chromatin then leaks into the cytosol, causing severe inflammation and cardiac dysfunction. Although SOH disruption was accompanied by loosened higher-order genomic structures, the change in gene expression before nuclear deformation was mild, suggesting that SOH play major roles in nuclear structural integrity. Aged CM nuclei consistently exhibited scattered SOH and marked elongation. Furthermore, we provide mechanistic insight into the development and maintenance of SOH driven by chromatin compaction and condensate formation. These results highlight SOH as a safeguard of nuclear shape and genomic integrity against mechanical stress. |
| format | Article |
| id | doaj-art-8ae6e71d01dd4681aaaba4f71d36cebc |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-8ae6e71d01dd4681aaaba4f71d36cebc2024-12-11T05:56:08ZengElsevierCell Reports2211-12472024-12-014312115048Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stressKeita Fujiwara0Tadashi Inoue1Aya Kimoto2Jiang Zixian3Keizo Tokuhiro4Yoshiki Yasukochi5Tomoya O. Akama6Chen-Leng Cai7Ichiro Shiojima8Hiroshi Kimura9Shige H. Yoshimura10Tomoyuki Nakamura11Maretoshi Hirai12Department of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; Department of Medicine II, Kansai Medical University, Hirakata, Osaka 573-1010, JapanDepartment of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanSchool of Life Science and Technology, Institute of Science Tokyo, Yokohama 226-8501, JapanLaboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanDepartment of Genome Editing, Institute of Biological Sciences, Kansai Medical University, Hirakata, Osaka 573-1010, JapanDepartment of Genome Analysis, Institute of Biological Sciences, Kansai Medical University, Hirakata, Osaka 573-1010, JapanDepartment of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangdong 510530, ChinaDepartment of Medicine II, Kansai Medical University, Hirakata, Osaka 573-1010, JapanSchool of Life Science and Technology, Institute of Science Tokyo, Yokohama 226-8501, Japan; Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo, Yokohama 226-8503, JapanLaboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanDepartment of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanDepartment of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; Corresponding authorSummary: Cardiomyocyte (CM) nuclei are constantly exposed to mechanical stress, but how they maintain their nuclear shape remains unknown. In this study, we found that ventricular CM nuclei acquire characteristic prominent spatial organizations of heterochromatin (SOH), which are disrupted by high-level expression of H2B-mCherry in mice. SOH disruption was associated with nuclear softening, leading to extreme elongation and rupture under unidirectional mechanical stress. Loosened chromatin then leaks into the cytosol, causing severe inflammation and cardiac dysfunction. Although SOH disruption was accompanied by loosened higher-order genomic structures, the change in gene expression before nuclear deformation was mild, suggesting that SOH play major roles in nuclear structural integrity. Aged CM nuclei consistently exhibited scattered SOH and marked elongation. Furthermore, we provide mechanistic insight into the development and maintenance of SOH driven by chromatin compaction and condensate formation. These results highlight SOH as a safeguard of nuclear shape and genomic integrity against mechanical stress.http://www.sciencedirect.com/science/article/pii/S2211124724013998CP: Cell biology |
| spellingShingle | Keita Fujiwara Tadashi Inoue Aya Kimoto Jiang Zixian Keizo Tokuhiro Yoshiki Yasukochi Tomoya O. Akama Chen-Leng Cai Ichiro Shiojima Hiroshi Kimura Shige H. Yoshimura Tomoyuki Nakamura Maretoshi Hirai Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress Cell Reports CP: Cell biology |
| title | Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| title_full | Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| title_fullStr | Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| title_full_unstemmed | Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| title_short | Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| title_sort | spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724013998 |
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