Identification of trophoblast‐specific elements in the HLA‐C core promoter

• Published in: HLA : immune response genetics 2018-11, Vol.92 (5), p.288-297
• Main Authors: Johnson, Jenna K., Wright, Paul W., Li, Hongchuan, Anderson, Stephen K.
• Format: Article
• Language: English
• Subjects: extravillous trophoblasts; HLA; HLA‐C; major histocompatibility complex; MHC class I; promoter; transcription factors
• ISSN: 2059-2302; 2059-2310
• DOI: 10.1111/tan.13404

There are several aspects of HLA‐C gene expression that distinguish it from the HLA‐A and HLA‐B genes. First, HLA‐C is expressed by extravillous trophoblasts, whereas HLA‐A and HLA‐B are not. Second, its cell‐surface expression is much lower, which has been linked to changes in transcription and efficiency of peptide loading and export. Third, HLA‐C possesses a NK cell‐specific promoter and a complex alternative splicing system that regulates expression during NK cell development. In this study, we investigate the contribution of the HLA‐C core promoter to trophoblast‐specific expression. Analysis of transcription start sites showed the presence of a trophoblast‐associated start site and additional upstream TATA and CCAAT‐box elements in the HLA‐C promoter, suggesting the presence of an overlapping trophoblast‐specific promoter. A comparison of in vitro promoter activity showed that the HLA‐C promoter was more active in trophoblast cell lines than either the HLA‐A or HLA‐B promoters. Enhanced trophoblast activity was mapped to the central enhanceosome region of the promoter, and mutational analysis identified changes in the RFX‐binding region that generated a trophoblast‐specific enhancer.