NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells

J Biol Chem. 2010 Mar 12;285(11):8256-67. doi: 10.1074/jbc.M109.041004. Epub 2010 Jan 5.


Expression of the cytokine interleukin-13 (IL13) is critical for Th2 immune responses and Th2-mediated allergic diseases. Activation of human IL13 expression involves chromatin remodeling and formation of multiple DNase I-hypersensitive sites throughout the locus. Among these, HS4 is detected in the distal IL13 promoter in both naive and polarized CD4(+) T cells. We show herein that HS4 acts as a position-independent, orientation-dependent positive regulator of IL13 proximal promoter activity in transiently transfected, activated human CD4(+) Jurkat T cells and primary murine Th2 cells. The 3'-half of HS4 (HS4-3') was responsible for IL13 up-regulation and bound nuclear factor (NF) 90 and NF45, as demonstrated by DNA affinity chromatography coupled with tandem mass spectrometry, chromatin immunoprecipitation, and gel shift analysis. Notably, the CTGTT NF45/NF90-binding motif within HS4-3' was critical for HS4-dependent up-regulation of IL13 expression. Moreover, transfection of HS4-IL13 reporter vectors into primary, in vitro differentiated Th2 cells from wild-type, NF45(+/-), or NF90(+/-) mice showed that HS4 activity was exquisitely dependent on the levels of endogenous NF45 (and to a lesser degree NF90), because HS4-dependent IL13 expression was virtually abrogated in NF45(+/-) cells and reduced in NF90(+/-) cells. Collectively, our results identify NF45 and NF90 as novel regulators of HS4-dependent human IL13 transcription in response to T cell activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Gene Expression / immunology
  • Genetic Complementation Test
  • Humans
  • Interleukin-13 / genetics*
  • Jurkat Cells
  • Lymphocyte Activation / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Nuclear Factor 45 Protein / metabolism*
  • Nuclear Factor 90 Proteins / metabolism*
  • Phosphorylation / immunology
  • Promoter Regions, Genetic / immunology
  • Th2 Cells / physiology*
  • Transcription, Genetic / immunology
  • Up-Regulation / immunology


  • ILF2 protein, human
  • ILF3 protein, human
  • Ilf2 protein, mouse
  • Interleukin-13
  • Nuclear Factor 45 Protein
  • Nuclear Factor 90 Proteins