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Emerin modulates spatial organization of chromosome territories in cells on softer matrices.

Published version
Peer-reviewed

Type

Article

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Authors

Pradhan, Roopali 
Ranade, Devika 

Abstract

Cells perceive and relay external mechanical forces into the nucleus through the nuclear envelope. Here we examined the effect of lowering substrate stiffness as a paradigm to address the impact of altered mechanical forces on nuclear structure-function relationships. RNA sequencing of cells on softer matrices revealed significant transcriptional imbalances, predominantly in chromatin associated processes and transcriptional deregulation of human Chromosome 1. Furthermore, 3-Dimensional fluorescence in situ hybridization (3D-FISH) analyses showed a significant mislocalization of Chromosome 1 and 19 Territories (CT) into the nuclear interior, consistent with their transcriptional deregulation. However, CT18 with relatively lower transcriptional dysregulation, also mislocalized into the nuclear interior. Furthermore, nuclear Lamins that regulate chromosome positioning, were mislocalized into the nuclear interior in response to lowered matrix stiffness. Notably, Lamin B2 overexpression retained CT18 near the nuclear periphery in cells on softer matrices. While, cells on softer matrices also activated emerin phosphorylation at a novel Tyr99 residue, the inhibition of which in a phospho-deficient mutant (emerinY99F), selectively retained chromosome 18 and 19 but not chromosome 1 territories at their conserved nuclear locations. Taken together, emerin functions as a key mechanosensor, that modulates the spatial organization of chromosome territories in the interphase nucleus.

Description

Keywords

Biomechanical Phenomena, Cell Line, Tumor, Cell Nucleus, Chromosome Positioning, Chromosomes, Human, Chromosomes, Human, Pair 18, Gene Expression Regulation, Histone Code, Humans, Lamin Type B, Lamins, Membrane Proteins, Nuclear Proteins, Phosphorylation, Transcription, Genetic, Tyrosine

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

46

Publisher

Oxford University Press (OUP)