Yin-Yang 1 and Yin-Yang 2 exert opposing effects on the promoter activity of interleukin 4

Arch Pharm Res. 2016 Apr;39(4):547-554. doi: 10.1007/s12272-015-0622-7. Epub 2015 Sep 7.

Abstract

Interleukin (IL)-4 acts on T cells as a growth and activation factor, and promotes the differentiation of type 2 T helper cells. In T cells, expression of the gene encoding IL-4 is regulated by inducible or constitutive factors. Yin-Yang (YY)-1 is one of constitutive transcription factors binding to the IL-4 promoter. The recently identified YY2 protein is similar to YY1, with both sharing high levels of homology in their zinc finger motifs. However, the role of YY2 in T cells is unclear. YY1 and YY2 were constitutively expressed in EL4 T cells, and their expression was not dependent on stimulation. IL-4 promoter (-741/+56 fragment) activity was enhanced by YY1, but inhibited by YY2. The enhanced IL-4 promoter activity by YY1 was reduced by simultaneous expression of YY2. In addition, the DNA binding affinity of YY1 to the IL-4 promoter was adversely affected by YY2. Our results suggest that YY1 and YY2 exert opposing effects on the IL-4 promoter as they compete for the same DNA binding sites.

Keywords: Constitutive factor; IL-4; Th2 cell; YY1; YY2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism
  • Luciferases, Firefly / genetics
  • Mice
  • Promoter Regions, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism*
  • Zinc Fingers / genetics

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • YY1 Transcription Factor
  • YY2 protein, mouse
  • Yy1 protein, mouse
  • Interleukin-4
  • Luciferases, Firefly