GAS elements: a few nucleotides with a major impact on cytokine-induced gene expression

Gamma interferon activation site (GAS) elements are short stretches of DNA, originally defined as a requirement for the rapid transcriptional induction of genes in response to interferon-gamma (IFN-gamma). The protein complex binding to GAS sequences in IFN-gamma-treated cells, the gamma interferon activation factor (GAF), is a dimer of Stat1, the prototype of a family of cytokine-responsive transcription factors, the signal transducers and activators of transcription. To date, seven different Stats are known (excluding alternatively spliced or processed forms), six of which recognize the same small palindromic consensus sequence TTCN2-4 GAA that defines a GAS element. Because one or several Stats take part in nuclear signaling in response to most cytokines or growth factors, the GAS sequence has changed from being viewed as a specific site for IFN-activated GAF to becoming the general nuclear end of the Jak-Stat signaling pathways. This review focuses on the identification and definition of GAS elements, their interaction with Stat transcription factors, and their contribution to the specificity of cytokine-induced gene expression.