Journal Article

Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes

Arumugam, Thilona, Adimulam, Theolan, Gokul, Anmol, Ramsuran, Veron

2024

Overview

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 modeling 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antigen presentation / Binding sites / Cancer / Cell activation / Chromatin / Cytotoxicity / Disease / DNA Methylation / Epigenesis, Genetic / Epigenetics / Gene expression / Gene Expression Regulation / Gene regulation / Genetic diversity / Genetic Variation / Genomes / Histocompatibility antigen HLA / HLA Antigens - genetics / human leukocyte antigen system (HLA) / Humans / Immunology / Influence / Leukocytes / Lymphocytes / Lymphocytes T / major histocompatibility complex (MHC) / MicroRNAs - genetics / miRNA / non-coding RNA / Nucleotide sequence / Peptides / Polymorphism / Polymorphism, Single Nucleotide / Proteins / RNA, Untranslated - genetics / single nucleotide polymorphisms (SNP) / Single-nucleotide polymorphism / Therapeutic applications / Transcription factors