Anergy is induced in T cells as a consequence of a partial or suboptimal 
stimulation. Anergic T cells become unresponsive and fail to proliferate and 
produce cytokines. We had previously shown that in anergic CD4(+) T cells, 
Ikaros participates in the transcriptional repression of the Il2 gene by 
recruiting histone deacetylases that cause core histone deacetylation at the Il2 
promoter. Here we show that deacetylation at the Il2 promoter is the initial 
step in a process that leads to the stable silencing of the Il2 gene 
transcription in anergic T cells. We have found that anergy-induced 
deacetylation of the Il2 promoter permits binding of the histone 
methyl-transferase Suv39H1, which trimethylates lysine-9 of histone H3 
(Me3H3-K9). Furthermore, the establishment of the Me3H3-K9 mark allows the 
recruitment of the heterochromatin protein HP1, allowing the silenced Il2 loci 
to reposition close to heterochromatin-rich regions. Our results indicate that 
silencing of Il2 transcription in anergic T cells is attained through a series 
of epigenetic changes that involve the establishment of repressive marks and the 
subsequent nuclear repositioning of the Il2 loci, which become juxtaposed to 
transcriptionally silent regions. This mechanism may account for the stable 
nature of the inhibition of IL-2 production in anergic cells.