Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms
Journal
Epigenetics and Chromatin
Journal Volume
15
Journal Issue
1
Date Issued
2022
Author(s)
Abstract
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. ? 2021, The Author(s).
Subjects
Nuclear envelope
Nuclear lamina
Nuclear morphology
TGFβ1
histone
histone H1
histone H3
lamin A
lamin B
nuclear protein
protein histone H3.3
protein lamin B1
protein SUN1
Smad protein
transforming growth factor beta1
unclassified drug
isoprotein
animal cell
Article
cell nuclear structure
cell nucleus membrane
chromatin structure
enzyme activation
Huh-7 cell line
human
human cell
mouse
nonhuman
nuclear lamina
nucleosome
protein expression
Smad signaling
upregulation
cell nucleus
Cell Nucleus
Histones
Nuclear Envelope
Nuclear Lamina
Protein Isoforms
SDGs
Type
journal article