Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs.
Acetylation of a transcription factor has recently been shown to play a significant role in gene regulation. Here we show that GATA-3 is acetylated in T cells and that a mutation introduced into amino acids 305-307 (KRR-GATA3) creates local hypoacetylation in GATA-3. Remarkably, KRR-GATA3 possesses the most potent suppressive effect when compared with other mutants that are disrupted in putative acetylation targets. Expressing this mutant in peripheral T cells results in defective T-cell homing to systemic lymphnodes, and prolonged T-cell survival after activation. These findings have significant implications in that the acetylation state of GATA-3 affects its physiological function in the immune system and, more importantly, provides evidence for the novel role of GATA-3 in T-cell survival and homing to secondary lymphoid organs.
Yamagata
T
T
Department of Hematology and Oncology, and Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Mitani
K
K
Oda
H
H
Suzuki
T
T
Honda
H
H
Asai
T
T
Maki
K
K
Nakamoto
T
T
Hirai
H
H
D000107:Acetylation; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D007376:Interleukin-2 / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000737:chemistry*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015534:Trans-Activators