CD28 costimulation controls histone hyperacetylation of the interleukin 5 gene locus in developing th2 cells.
Interleukin 5 (IL-5) plays a unique role in allergic inflammatory responses, and the understanding of molecular mechanisms underlying the generation of IL-5-producing cells is crucial for the regulation of allergic disorders. Differentiation of naive CD4 T cells into type-2 helper (Th2) cells is accompanied by chromatin remodeling including hyperacetylation of histones H3 and H4 in the nucleosomes associated with the IL-4, IL-13, and IL-5 genes. Histone hyperacetylation of the IL-5 gene displayed a delayed kinetics compared with that of the IL-4 and IL-13 genes, suggesting a distinct remodeling mechanism for the IL-5-gene locus. Here we studied the role of CD28 costimulation in the generation of IL-5-producing cells and the histone hyperacetylation of the IL-5 gene locus. CD28-costimulation selectively enhanced histone hyperacetylation of the IL-5 gene locus that appeared to be mediated through NF-kappaB activation and subsequent up-regulation of GATA3. The CD28 costimulation-sensitive histone hyperacetylation spanned almost the entire intergenic region between the IL-5 and RAD50 accompanied with intergenic transcript. Thus, this is the first demonstration that CD28 costimulation controls a chromatin-remodeling process during Th2 cell differentiation.
Inami
Masamichi
M
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
Yamashita
Masakatsu
M
Tenda
Yoshiyuki
Y
Hasegawa
Akihiro
A
Kimura
Motoko
M
Hashimoto
Kahoko
K
Seki
Nobuo
N
Taniguchi
Masaru
M
Nakayama
Toshinori
T
D000107:Acetylation; D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D004260:DNA Repair; D006657:Histones / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D018106:CD28 Antigens; D006657:Histones; D015848:Interleukin-5