Yin-Yang 1 activates interleukin-4 gene expression in T cells.
Interleukin-4 (IL-4) is a multifunctional cytokine that plays an important role in immune and inflammatory responses. Expression of the IL-4 gene is tightly controlled at the level of gene transcription by both positive and negative regulatory elements in the IL-4 promoter. Several constitutive nuclear factors have been identified that can interact with IL-4 promoter elements in DNA binding assays. Here we report that the zinc-finger protein YY-1 (Yin-Yang 1) can bind to multiple elements within the human IL-4 promoter. Cotransfection of Jurkat T cells with different IL-4 promoter/reporter constructs together with expression vectors encoding antisense, wild-type, or zinc finger-deleted mutant YY-1 suggested that YY-1 enhanced IL-4 promoter activity in a DNA-binding domain-dependent manner. Site-directed mutagenesis revealed that a proximal YY-1-binding site, termed Y0 ((-59)TCATTTT(-53)), was essential for YY-1-driven IL-4 promoter activity. In addition, cotransfected YY-1 enhanced both IL-4 promoter activity and endogenous IL-4 gene expression in nontransformed peripheral blood T cells. Thus, YY-1 positively regulates IL-4 gene expression in lymphocytes.
Guo
J
J
Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
Casolaro
V
V
Seto
E
E
Yang
W M
WM
Chang
C
C
Seminario
M C
MC
Keen
J
J
Georas
S N
SN
D000001:Calcimycin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D050986:YY1 Transcription Factor; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D007476:Ionophores; D009687:Nuclear Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D015847:Interleukin-4; D000001:Calcimycin