Integrin a4ß1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration

Author(s): Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, et al.

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 α4β1 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 α4β1 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 α4β1 integrin signaling drives specific chromatin modifications, which alter the physical properties of the nucleus and thereby enable T-cell migration.

Similar Articles

A ras-related gene with transformation suppressor activity

Author(s): Kitayama H, Matsuzaki T, Ikawa Y, Noda M

Rap1A deficient T and B cells show impaired integrin-mediated cell adhesion

Author(s): Duchniewicz M, Zwartkruis T, Kolanczyk M

Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis

Author(s): Carmona G, Göttig S, Orlandi A, Scheele J, Bäuerle T, et al

A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development

Author(s): Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, et al.

Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes

Author(s): Awasthi A, Samarakoon A, Chu H,Kamalakannan R, Quilliam LA, et al.

CalDAG-GEFI in LFA-1 but not VLA-4 integrin-mediated human T-cell adhesion

Author(s): Ghandour H, Cullere X, Alvarez A , Luscinskas FW, Mayadas TN

RapGEF2 is essential for embryonic hematopoiesis but dispensable for adult hematopoiesis

Author(s): Satyanarayana A, Gudmundsson KO, Chen X, Coppola V, Tessarollo L, et al.

Activation of Epac stimulates integrin-dependent homing of progenitor cells

Author(s): Carmona G, Chavakis E, Koehl U, Zeiher AM, Dimmeler S

Rasa3 controls megakaryocyte Rap1 activation, integrin signaling and differentiation into proplatelet

Author(s): Molina-Ortiz P, Polizzi S, Ramery E, Gayral S, Delierneux C, et al.

Methyltransferase G9A regulates T cell differentiation during murine intestinal inflammation

Author(s): Antignano F, Burrows K, Hughes MR, Han JM, Kron KJ, et al.

G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

Author(s): Zhang T, Termanis A, Özkan B, Bao XX, Culley J, et al.