The final, formatted version of the article will be published soon.
REVIEW article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1422834
This article is part of the Research Topic Deciphering the Intricate Relationship between Epigenetics and Transcription in Immune System Regulation View all 4 articles
Variation within the Non-Coding Genome Influences Genetic and Epigenetic Regulation of the Human Leukocyte Antigen Genes
Provisionally accepted- University of KwaZulu-Natal, Durban, South Africa
Variation within the non-coding genome may influence the regulation and expression of important genes involved in immune control such as the human leukocyte antigen (HLA) system. Class I and Class II HLA molecules are essential for peptide presentation which is required for T lymphocyte activation. Single nucleotide polymorphisms within non-coding regions of HLA Class I and Class II genes may influence the expression of these genes by affecting the binding of transcription factors and chromatin modelling molecules. Furthermore, an interplay between genetic and epigenetic factors may also influence HLA expression. Epigenetic factors such as DNA methylation and non-coding RNA, regulate gene expression without changing the DNA sequence. However, genetic variation may promote or allow genes to escape regulation by epigenetic factors, resulting in altered expression. The HLA system is central to most diseases, therefore, understanding the role of genetics and epigenetics on HLA regulation will tremendously impact healthcare. The knowledge gained from these studies may lead to novel and cost-effective diagnostic approaches and therapeutic interventions. This review discusses the role of non-coding variants on HLA regulation. Furthermore, we discuss the interplay between genetic and epigenetic factors on the regulation of HLA by evaluating literature based on polymorphisms within DNA methylation and miRNA regulatory sites within class I and Class II HLA genes. We also provide insight into the importance of the HLA non-coding genome on disease, discuss ethnic-specific differences across the HLA region and provide guidelines for future HLA studies.
Keywords: Human leukocyte antigen system (HLA), Major histocompatibility complex (MHC), Single Nucleotide Polymorphisms (SNP), epigenetics, DNA Methylation, non-coding RNA, microRNA
Received: 24 Apr 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Arumugam, Adimulam, Gokul and Ramsuran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Thilona Arumugam, University of KwaZulu-Natal, Durban, South Africa
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.