Integrin α4ß1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration.
Nucleic Acids Res
; 44(7): 3031-44, 2016 Apr 20.
Article
em En
| MEDLINE
| ID: mdl-26657637
ABSTRACT
The mechanical properties of the cell nucleus change to allow cells to migrate, but how chromatin modifications contribute to nuclear deformability has not been defined. Here, we demonstrate that a major factor in this process involves epigenetic changes that underpin nuclear structure. We investigated the link between cell adhesion and epigenetic changes in T-cells, and demonstrate that T-cell adhesion to VCAM1 via α4ß1 integrin drives histone H3 methylation (H3K9me2/3) through the methyltransferase G9a. In this process, active G9a is recruited to the nuclear envelope and interacts with lamin B1 during T-cell adhesion through α4ß1 integrin. G9a activity not only reorganises the chromatin structure in T-cells, but also affects the stiffness and viscoelastic properties of the nucleus. Moreover, we further demonstrated that these epigenetic changes were linked to lymphocyte movement, as depletion or inhibition of G9a blocks T-cell migration in both 2D and 3D environments. Thus, our results identify a novel mechanism in T-cells by which α4ß1 integrin signaling drives specific chromatin modifications, which alter the physical properties of the nucleus and thereby enable T-cell migration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Movimento Celular
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Núcleo Celular
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Histona-Lisina N-Metiltransferase
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Integrina alfa4beta1
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Epigênese Genética
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Antígenos de Histocompatibilidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Reino Unido