Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms

Epigenetics & Chromatin

Pen-Hsiu Grace Chao¹  Jing-Ya Wang²  Wan-Ping Wang²  Ming-Chun Hung²  Ya-Hui Chi³  Gunn-Guang Liou⁴ 

[1] Department of Biomedical Engineering, School of Medicine and School of Engineering, National Taiwan University, 10617, Taipei, Taiwan;Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Miaoli County, Taiwan;Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Miaoli County, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, 40402, Taichung, Taiwan;National Taiwan University College of Medicine, 10051, Taipei, Taiwan;

关键词: Nuclear envelope;    Nuclear lamina;    Nuclear morphology;    TGFβ1;   

DOI  :  10.1186/s13072-021-00434-3

来源: Springer

【 摘 要 】

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 TGFβ1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFβ1-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. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, clustering at the nuclear periphery and reintegrating into the nucleoplasm. 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 TGFβ1-induced compositional changes in the chromatin and nuclear lamina.

【 授权许可】

CC BY