Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements (95.4)

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (1_Supplement), p.95-95.4
• Main Authors: Chen, Qiaoyi, Zhang, Tao, Pincus, Seth, Wu, Shixiu, Ricks, David, Liu, Donald, Sun, Zhongsheng, Maclaren, Noel, Lan, Michael
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.95.4

CD1d expressing cells present lipid antigen to CD1d-restricted natural killer T (NKT) cells, which play an important role in immune regulation and tumor rejection. Lymphoid enhancer-binding factor-1 (LEF-1) is one of the regulators of the Wnt signaling pathway, which is a powerful regulator in cellular growth, differentiation, and transformation. There is little evidence connecting Wnt signaling to CD1d expression. In this study, we have identified LEF-1 as a regulator of the expression of the gene encoding the human CD1d molecule (CD1D). We found that LEF-1 binds specifically to the CD1D promoter. Over-expression of LEF-1 in K562 or Jurkat cells suppresses CD1D promoter activity and down regulates endogenous CD1D transcripts, whereas knockdown of LEF-1 using LEF-1-specific siRNA increases CD1D transcripts in K562 and Jurkat cells but different levels of surface CD1d on these two cell types. Chromatin immunoprecipitation showed that the endogenous LEF-1 factor is situated at the CD1D promoter and interacts with histone deacetylase-1 to facilitate the transcriptional repressor activity. Knockdown of LEF-1 using siRNA potentiates an acetylation state of histone H3/H4, supporting that LEF-1 acts as a transcriptional repressor for CD1D gene. Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of human CD1D gene.