Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus.
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.
Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Japan.
Masakatsu
M
Yamashita
Maki
M
Ukai-Tadenuma
Motoko
M
Kimura
Miyuki
M
Omori
Masamichi
M
Inami
Masaru
M
Taniguchi
Toshinori
T
Nakayama
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005091:Exons; D050990:GATA3 Transcription Factor; D006657:Histones / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009707:Nucleosomes / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D006657:Histones; D018793:Interleukin-13; D009707:Nucleosomes; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4