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Oct‐1 is responsible for the C‐33T polymorphism effect in the IL‐4 promoter
Author(s) -
Gervaziev Y. V.,
Olenina L. V.,
Krasotkina J. V.,
Lupatov A. Y.,
Mazurina S. A.,
Gervazieva V. B.
Publication year - 2010
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2009.00883.x
Subject(s) - genetics , promoter , polymorphism (computer science) , biology , gene , microbiology and biotechnology , genotype , gene expression
Summary IL‐4 is a pleiotropic immunoregulatory cytokine secreted by Th2 subset of CD4 + Th cells. Several transcription factors (TFs) have been determined with various degrees of certainty to bind the IL‐4 promoter and to regulate its expression in human. To investigate the mechanisms responsible for phenotypic effects of the C‐33T IL‐4 promoter polymorphism, we performed a search of TFs binding to this promoter locus and discriminating the −33C and −33T alleles. In silico searches suggest few factors bind this region. Using an electromobility shift assay we found that Jurkat T cells contained proteins which specifically interacted with oligonucleotide probes, corresponding to the −33 region. Considerable binding differences between C and T alleles were demonstrated using competitive conditions, the proteins bound predominantly with −33C allele. We found that the transcription factor Oct‐1 produced the major shifted complex. The binding of Oct‐1 was not improved using activated nuclear extracts; however, we observed increases in other shifted complexes upon cell activation. We suppose that Oct‐1 occupancy may compete for binding of activator proteins to closely or overlapped binding sites. Our findings suggest that the interplay between Oct‐1 and unknown TFs may be responsible for the C‐33T polymorphism effects.