Long-range regulation of cytokine gene expression.

In metazoans, transcription is regulated by promoters and additional elements, which may be located far from their target gene(s). Moreover, genes (including those encoding cytokines and cytokine receptors) are commonly clustered in the genome, providing the opportunity for the shared, competitive, or sequential use of regulatory elements. New techniques, discussed here, are generating an avalanche of high-resolution genome-wide data through which candidate regulatory elements have been identified in specific cell types (including T cells), their functions inferred, and their physical interactions in three-dimensional space demonstrated. As a result, a nearly comprehensive list of regulatory elements in the Th2 cytokine locus, a growing list of elements in the interferon-gamma gene locus, and maps of their three-dimensional interactions are now available, though much remains to be learned about the molecular mechanisms at play, the dynamics of these interactions, and their functional importance.