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| Status |
Public on Mar 09, 2015 |
| Title |
Histone Methyltransferase Ezh2 Controls Cell Adhesion and Migration through Direct Methylation of the Extra-Nuclear Protein-Talin |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Control and Ezh2-deficient bone marrow derived immature and mature dendritic cells were analyzed in triplicates
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| Contributor(s) |
Gunawan M, Venkatesan N, Loh JT, Wong JF, Berger HH, Neo WH, Li LY, Win MK, Yau YH, Guo T, See PC, Yamazaki S, Chin KC, Gingras A, Shochat SG, Ng LG, Sze SK, Ginhoux F, Su I |
| Citation(s) |
25751747 |
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| Submission date |
Aug 06, 2014 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Michael Poidinger |
| E-mail(s) |
michael_poidinger@immunol.a-star.edu.sg
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| Phone |
+6564070528
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| URL |
http://www.sign.a-star.edu.sg
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| Organization name |
Singapore Immunology Network
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| Department |
Bioinformatics
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| Street address |
#04-06, 8A Biomedical Grove
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| City |
Singapore |
| ZIP/Postal code |
138648 |
| Country |
Singapore |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA257565 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60146_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE60146_non-normalized.txt.gz |
3.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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