Identification of a Conserved GATA3 Response Element Upstream Proximal from the Interleukin-13 Gene Locus* 210

Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling of Th2 cytokine gene loci. Hyperacetylation of histone H3 on nucleosomes associated with the interleukin (IL)-4, IL-13 and IL-5 genes was observed in developing Th2 cells but not in Th1 cells. Histone hyperacetylation on IL-5 gene-associated nucleosomes was Th2-specific but occurred with delayed kinetics, and hyperacetylation on RAD50 gene-associated nucleosomes was T cell antigen receptor stimulation-dependent but not Th2-specific. The induction of the Th2-specific histone hyperacetylation was STAT6- and GATA3-dependent, and interestingly, it was accompanied by the expression of intergenic transcripts within the IL-13 and IL-4 gene loci. A conserved GATA3 response element (CGRE) containing four GATA consensus sequences was identified 1.6 kbp upstream from the IL-13 gene, corresponding with the 5′-border of the Th2-specific histone hyperacetylation region. The CGRE was shown to bind to GATA3, histone acetyltransferase complexes including CBP/p300, and RNA polymerase II. Also, the CGRE showed a significant enhancing effect on the Th2 cytokine gene promoters. Thus, the CGRE may play a crucial role for GATA3-mediated targeting and downstream spreading of core histone hyperacetylation within the IL-13 and IL-4 gene loci.

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