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/EBPβ 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/EBPβ. 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.