title: Nuclear factor of activated T cells 1 (NFAT1)-induced permissive chromatin modification facilitates nuclear factor-κB (NF-κB)-mediated interleukin-9 (IL-9) transactivation.
abstract: IL-9 regulates diverse inflammatory immune responses. Although the functional importance of IL-9 has been investigated in various pathophysiological conditions, molecular mechanisms by which TCR stimulation induced IL-9 gene expression are still unclear. In this study, we investigated the functional importance of the NFAT1 and NF-κB (p65) in IL-9 gene transcription in CD4(+) T cells. In vivo binding of NFAT1 and NF-κB (p65) to the IL-9 promoter was observed. NFAT1 binding induced a transcriptionally active chromatin configuration at the IL-9 promoter locus, whereas NF-κB (p65) binding transactivated the IL-9 promoter. Mouse deficient in NFAT1 shows a significant down-regulation of IL-9 expression that resulted from an inaccessible chromatin configuration at the IL-9 promoter. In parallel, knockdown of NF-κB (p65) also resulted in reduced IL-9 expression. In this process, NFAT1 plays a pivotal role as a core protein that creates an accessible platform for the assembly of transcription activators. The presence of NFAT1 correlates with recruitment of NF-κB (p65), p300, and active histone markers on the IL-9 promoter, resulting in a transcriptionally competent promoter. NFAT1 deficiency significantly reduced the recruitment of the above activation complex to the IL-9 promoter. In summary, our data suggest that functional cooperation of NFAT1 and NF-κB synergistically enhances IL-9 transcription in CD4(+) T cells.
authors.affiliation: School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Korea.
authors.forename: Arijita
authors.initials: A
authors.lastname: Jash
authors.forename: Anupama
authors.initials: A
authors.lastname: Sahoo
authors.forename: Gi-Cheon
authors.initials: GC
authors.lastname: Kim
authors.forename: Chang-Suk
authors.initials: CS
authors.lastname: Chae
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Hwang
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D016906:Interleukin-9 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012689:Sequence Homology, Nucleic Acid; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D016906:Interleukin-9; D050778:NFATC Transcription Factors; D051996:Transcription Factor RelA