Histone Methyltransferase Ezh2 Controls Cell Adhesion and Migration through Direct Methylation of the Extra-Nuclear Protein-Talin

ABSTRACT: Previously, we suggested a cytosolic role for the histone-methyltransferase Ezh2 in regulating lymphocyte activation, but molecular mechanisms underpinning this extra-nuclear function remained unclear. Here we show that Ezh2 regulates integrin-signaling and adhesion dynamics of neutrophils and dendritic cells. Ezh2 deficiency impaired integrin-dependent transendothelial migration of innate leukocytes and restricted disease progression in an animal model of multiple sclerosis. Direct methylation of talin, a key regulatory molecule in cell migration, by Ezh2 disrupted talin binding to F-actin and thereby promoted adhesion structure turnover. This regulatory effect was abolished by targeted disruption of Ezh2 interactions with Vav1. Our studies reveal a novel extra-nuclear function for Ezh2 in regulating adhesion dynamics with implications for leukocyte migration, immune responses and potentially pathogenic processes.

ORGANISM(S): Mus musculus

PROVIDER: GSE60146 | GEO | 2015/03/09

SECONDARY ACCESSION(S): PRJNA257565

REPOSITORIES: GEO