Dress codes are often used by exclusive restaurants to prevent undesirable clientele lowering the tone of their premises. In the same way, chromatin codes, defined by patterns of histone modifications such as acetylation and methylation, dictate whether a gene locus is open (allowing for transcription), or closed (meaning transcription is inhibited). T-cell receptor (TCR) rearrangement, which occurs during thymocyte development and enables a broad range of TCR specificities to be generated, might also be affected by chromatin codes. An open structure might allow access for recombination-activating gene (RAG) products, in a similar way as it does for transcriptional machinery.

Interleukin-7 (IL-7) is required for normal lymphoid development and survival, and for rearrangement at the TCRγ locus, but the mechanism of its action in this process is unknown. Two reports, from Muegge's group in The Journal of Immunology, and from Ikuta's laboratory in Immunity, now show that IL-7 signalling regulates TCRγ gene rearrangement by specifically altering histone acetylation within the TCRγ locus.

Both groups performed chromatin-immunoprecipitation (ChIP) analysis to study the acetylation status of histones 3 and 4 within regulatory sites of the TCRγ locus in thymocytes from wild-type and IL-7 receptor-α ( Il7Rα )−/− mice. Acetylation of histone tails is thought to result in an open chromatin structure. Muegge and colleagues found that, in comparison with other sites within the genome, histone acetylation of the TCRγ locus was enhanced in wild-type thymocytes. Results from both groups showed that this hyperacetylation was not seen in thymocytes from Il7Rα−/− mice, indicating that the specific acetylation of the TCRγ locus is dependent on IL-7 signalling.

Does IL-7 have a direct effect on accessibility at the TCRγ locus? Muegge and colleagues investigated this by treating thymocytes from Il7−/− Rag2 −/− mice with IL-7, and assessing the production of constant-region transcripts. Crossing Il7−/− mice with Rag2−/− mice was necessary as Il7−/− thymi are arrested in γδ T-cell development, but show substantial leakiness in αβ T-cell development. Within 5 hours of IL-7 treatment, constant-region transcripts were induced in thymocytes from double-knockout mice, indicating that IL-7 signalling is directly able to open chromatin in thymocyte precursors. The authors went on to show that this IL-7-inducible chromatin opening in Il7−/−Rag2−/− thymocytes was due to increased acetylation of histones within the TCRγ locus.

Previous work form Ikuta's group has implicated the transcription factor Stat5 in IL-7-mediated control of TCRγ locus accessibility. To see if Stat5 acts by controlling histone acetylation of this locus, ChIP assays were performed with Il7Rα−/− thymocytes cultured with or without Stat5 cDNAs. Introduction of active Stat5 restored the histone acetylation and accessibility of the TCRγ locus in Il7Rα−/− thymocytes. Ikuta and colleagues concluded that cytokine signalling results in recruitment of Stat5, which, in turn, recruits transcriptional co-activators, and controls the accessibility of the TCRγ locus by histone acetylation. These studies of the TCRγ locus are the first to directly link an extracellular stimulus to changes in chromatin structure.