Deformation of the Nucleus by TGFβ1 Via the Remodeling of Nuclear Envelope and Histone Isoforms
| Autor: | Ya-Hui Chi, Ming-Chun Hung, Pen-Hsiu Grace Chao, Gunn-Guang Liou, Jing-Ya Wang, Wan-Ping Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Cell Nucleus Nuclear Lamina biology Chemistry Nuclear Envelope Research Nuclear morphology TGFβ1 Deformation (meteorology) QH426-470 Histones medicine.anatomical_structure Histone Cell Line Tumor medicine Biophysics biology.protein Genetics Humans Protein Isoforms Nucleus Molecular Biology Envelope (waves) |
| Zdroj: | Epigenetics & Chromatin, Vol 15, Iss 1, Pp 1-17 (2022) Epigenetics & Chromatin |
| DOI: | 10.21203/rs.3.rs-944682/v1 |
| Popis: | The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina. |
| Databáze: | OpenAIRE |
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