| First Author | Serrat N | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 11 | Pages | 3028-37 |
| PubMed ID | 22865229 | Mgi Jnum | J:188782 |
| Mgi Id | MGI:5442227 | Doi | 10.1002/eji.201242413 |
| Citation | Serrat N, et al. (2012) Deacetylation of C/EBPbeta is required for IL-4-induced arginase-1 expression in murine macrophages. Eur J Immunol 42(11):3028-37 |
| abstractText | The amount of arginine available at inflammatory loci is a limiting factor for the growth of several cells of the immune system. IL-4-induced activation of macrophages produced arginase-1, which converts arginine into ornithine, a precursor of polyamines and proline. Trichostatin A (TSA), a pan-inhibitor of histone deacetylases (HDACs), inhibited IL-4-induced arginase-1 expression. TSA showed promoter-specific effects on the IL-4-responsive genes. While TSA inhibited the expression of arginase-1, fizz1, and mrc1, other genes, such as ym,1 mgl1, and mgl2, were not affected. The inhibition of arginase-1 occurred at the transcriptional level with the inhibition of polymerase II binding to the promoter. IL-4 induced STAT6 phosphorylation and binding to DNA. These activities were not affected by TSA treatment. However, TSA inhibited C/EBPbeta DNA binding. This inhibitor induced acetylation on lysine residues 215-216, which are critical for DNA binding. Finally, using macrophages from STAT6 KO mice we showed that STAT6 is required for the DNA binding of C/EBPbeta. These results demonstrate that the acetylation/deacetylation balance strongly influences the expression of arginase-1, a gene of alternative activation of macrophages. These findings also provide a molecular mechanism to explain the control of gene expression through deacetylase activity. |
