Abstract
Class Ia molecules of human leucocyte antigen (HLA-A, -B and -C) are widely expressed and play a central role in the immune system by presenting peptides derived from the lumen of the endoplasmic reticulum. In contrast, class Ib molecules such as HLA-G serve novel functions. The distribution of HLA-G is mostly limited to foetal trophoblastic tissues and some tumour tissues. The mechanism required for the tissue-specific regulation of the HLA-G gene has not been well understood. Here, we investigated the genomic regulation of HLA-G by manipulating one copy of a genomic DNA fragment on a human artificial chromosome. We identified a potential negative regulator of gene expression in a sequence upstream of HLA-G that overlapped with the long interspersed element (LINE1); silencing of HLA-G involved a DNA secondary structure generated in LINE1. The presence of a LINE1 gene silencer may explain the limited expression of HLA-G compared with other class I genes.
Highlights
Class Ia molecules of human leucocyte antigen (HLA-A, -B and -C) and class Ib molecules (HLA-E, -F and -G) are members of human major histocompatibility complex (MHC), a cell surface molecule encoded by gene family
We identified a negative regulator of gene expression in a sequence upstream of HLA-G that overlapped with a LINE1 sequence
We investigated the genomic regulation of HLA-G using a human artificial chromosome (HAC) vector, identifying a negative regulator of gene expression in a sequence upstream of HLA-G that overlapped with a LINE1 sequence
Summary
Class Ia molecules of human leucocyte antigen (HLA-A, -B and -C) and class Ib molecules (HLA-E, -F and -G) are members of human major histocompatibility complex (MHC), a cell surface molecule encoded by gene family. Class Ia molecules are widely expressed in tissues and play a central role in the immune system by presenting peptides derived from the lumen of the endoplasmic reticulum [1]. The class Ib molecule HLA-G contributes to maternal tolerance of the allogeneic foetus and to novel functions [2,3]. HLA family genes were derived from gene duplication, accompanied by the insertion of retrotransposons [6,7]. The sequences upstream [50] and downstream [30] of the coding region are analogous among HLA genes, they are often interrupted by highly abundant retrotransposons, including long interspersed elements (LINE1 or L1) [8,9]. Tissue-specific regulation of the HLA-G gene is not well understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
