Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction
Aberrant nuclear morphology is a hallmark of human disease and causes nuclear dysfunction. Perturbed nuclear mechanics via reduced heterochromatin weakens the nucleus resulting in nuclear blebbing and rupture. While the role of heterochromatin is known, the separate roles of constitutive heterochrom...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Nucleus |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19491034.2025.2486816 |
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| author | Gianna Manning Andy Li Nebiyat Eskndir Marilena Currey Andrew D. Stephens |
| author_facet | Gianna Manning Andy Li Nebiyat Eskndir Marilena Currey Andrew D. Stephens |
| author_sort | Gianna Manning |
| collection | DOAJ |
| description | Aberrant nuclear morphology is a hallmark of human disease and causes nuclear dysfunction. Perturbed nuclear mechanics via reduced heterochromatin weakens the nucleus resulting in nuclear blebbing and rupture. While the role of heterochromatin is known, the separate roles of constitutive heterochromatin methylation states remains elusive. Using MEF and HT1080 cells, we isolated the individual contribution of constitutive heterochromatin H3K9 methylation states through histone methyltransferase inhibitors. Inhibition of SUV39H1 via Chaetocin downregulates H3K9 trimethylation (me3), while inhibition of G9a via BIX01294 downregulates H3K9 dimethylation (me2). Overall, the loss of H3K9me3 increased nuclear blebbing and rupture in interphase nuclei due to decreased nuclear rigidity from decompaction of chromocenters. Oppositely, loss of H3K9me2 decreased nuclear blebbing and rupture with increased nuclear rigidity and more compact chromocenters. We show that facultative heterochromatin and HP1α are non-essential for chromocenter compaction. Constitutive heterochromatin provides essential nuclear mechanical support to maintain nuclear shape and integrity through chromocenter compaction. |
| format | Article |
| id | doaj-art-f315e5c882ca441fa8432d80ca92c556 |
| institution | DOAJ |
| issn | 1949-1034 1949-1042 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Nucleus |
| spelling | doaj-art-f315e5c882ca441fa8432d80ca92c5562025-08-20T03:08:36ZengTaylor & Francis GroupNucleus1949-10341949-10422025-12-0116110.1080/19491034.2025.2486816Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compactionGianna Manning0Andy Li1Nebiyat Eskndir2Marilena Currey3Andrew D. Stephens4Biology Department, University of Massachusetts Amherst, Amherst, MA, USABiology Department, University of Massachusetts Amherst, Amherst, MA, USABiology Department, University of Massachusetts Amherst, Amherst, MA, USABiology Department, University of Massachusetts Amherst, Amherst, MA, USABiology Department, University of Massachusetts Amherst, Amherst, MA, USAAberrant nuclear morphology is a hallmark of human disease and causes nuclear dysfunction. Perturbed nuclear mechanics via reduced heterochromatin weakens the nucleus resulting in nuclear blebbing and rupture. While the role of heterochromatin is known, the separate roles of constitutive heterochromatin methylation states remains elusive. Using MEF and HT1080 cells, we isolated the individual contribution of constitutive heterochromatin H3K9 methylation states through histone methyltransferase inhibitors. Inhibition of SUV39H1 via Chaetocin downregulates H3K9 trimethylation (me3), while inhibition of G9a via BIX01294 downregulates H3K9 dimethylation (me2). Overall, the loss of H3K9me3 increased nuclear blebbing and rupture in interphase nuclei due to decreased nuclear rigidity from decompaction of chromocenters. Oppositely, loss of H3K9me2 decreased nuclear blebbing and rupture with increased nuclear rigidity and more compact chromocenters. We show that facultative heterochromatin and HP1α are non-essential for chromocenter compaction. Constitutive heterochromatin provides essential nuclear mechanical support to maintain nuclear shape and integrity through chromocenter compaction.https://www.tandfonline.com/doi/10.1080/19491034.2025.2486816Chromocenterheterochromatinnuclear blebbingnuclear mechanicsnuclear structure |
| spellingShingle | Gianna Manning Andy Li Nebiyat Eskndir Marilena Currey Andrew D. Stephens Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction Nucleus Chromocenter heterochromatin nuclear blebbing nuclear mechanics nuclear structure |
| title | Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction |
| title_full | Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction |
| title_fullStr | Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction |
| title_full_unstemmed | Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction |
| title_short | Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction |
| title_sort | constitutive heterochromatin controls nuclear mechanics morphology and integrity through h3k9me3 mediated chromocenter compaction |
| topic | Chromocenter heterochromatin nuclear blebbing nuclear mechanics nuclear structure |
| url | https://www.tandfonline.com/doi/10.1080/19491034.2025.2486816 |
| work_keys_str_mv | AT giannamanning constitutiveheterochromatincontrolsnuclearmechanicsmorphologyandintegritythroughh3k9me3mediatedchromocentercompaction AT andyli constitutiveheterochromatincontrolsnuclearmechanicsmorphologyandintegritythroughh3k9me3mediatedchromocentercompaction AT nebiyateskndir constitutiveheterochromatincontrolsnuclearmechanicsmorphologyandintegritythroughh3k9me3mediatedchromocentercompaction AT marilenacurrey constitutiveheterochromatincontrolsnuclearmechanicsmorphologyandintegritythroughh3k9me3mediatedchromocentercompaction AT andrewdstephens constitutiveheterochromatincontrolsnuclearmechanicsmorphologyandintegritythroughh3k9me3mediatedchromocentercompaction |