Publications by authors named "Junggang Li"

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The role of upstream stimulatory factor 1 in the transcriptional regulation of the human TBX21 promoter mediated by the T-1514C polymorphism associated with systemic lupus erythematosus.

Immunogenetics 2012 May 19;64(5):361-70. Epub 2012 Jan 19.

Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

T-bet is a key regulator for the lineage commitment in CD4+ T helper (Th) 1 cells by activating the hallmark production of interferon-γ. Previously, two single nucleotide polymorphisms (SNPs) in the TBX21 promoter, T-1993C and T-1514C, have been shown by statistic studies to associate with systemic lupus erythematosus (SLE). The effect of -1993 SNP on the Yin Yang 1 transcription factor-mediated promoter activity has been already indicated. This study aimed to investigate roles of the T-1514C SNP on TBX21 transcription and its functional effect by luciferase reporter, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, and flow cytometric analysis of intracellular T-bet, IFN-γ, and IL-4 expression in activated CD4+ T cells. The TBX21 promoter carrying -1514C possessed significantly lower transcriptional activity than that of -1514T and was markedly downregulated by the overexpression of upstream stimulatory factor 1 (USF-1) when compared with the promoter carrying -1514T. EMSA indicated that the transcription factor USF-1 was bound to the -1514C allele probe with the affinity higher than that to the -1514T allele probe. ChIP assay suggested that USF-1 bound around -1514 of TBX21 genomic DNA in vivo in the human T cell line Jurkat with -1514C/T. The individuals carrying -1514C allele were determined to have significantly diminished expression of T-bet and IFN-γ and increased IL-4 production in CD4+ T cells compared with those of -1514T allele. The findings demonstrate that the T-1514C polymorphism affects TBX21 gene expression and Th1 cytokine production by binding USF-1 to the SNP site.
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http://dx.doi.org/10.1007/s00251-011-0597-6DOI Listing
May 2012