Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease

Abstract

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

“…DNA methylation is a biochemical process involving the addition of a methyl moiety to a cytosine or adenine residue at repeated CpG dinucleotides (CpG island) in gene promoter regions for repressing gene expression, which is part of the epigenetic regulation process of gene expression (Table 3) [63][64][65][66][67][68][69][70][71][72][73][74]. The biochemical process is mediated by DNA methyl-transferase (DNMT) 1, 3a, and 3b.…”

“…Coit et al [64] have even reported that CG10152449 in CHST 12 hypomethylation in CD4 + T cells has a very high specificity (64.3%) to the patients with lupus nephritis. De la Calle-Fabregat [70] concluded that DNA methylation is essential for immune differentiation, and its derangement is highly implicated in the development of this autoimmune disease. Zhang et al [71] found that IFI35 hypomethylation in CD3 + T cells can enhance the proliferation of mesangial cells relevant to lupus nephritis by deleting the methylation status of lupus kidneys.…”

Dim and Dmoc Protecting Groups for Oligodeoxynucleotide Synthesis

“…Under these conditions, many sensitive functionalities that cannot survive deprotection and cleavage conditions used in traditional ODN synthesis technologies but can co-exist with ODN can survive, thus, the Dim-Dmoc technology can be used to synthesize sensitive ODNs. We expect that the technology will find applications in many areas including developing new DNA and RNA cross-linking agents for applications such as antisense drug development, disease diagnosis, nucleic acidprotein interaction studies; and synthesizing sensitive model DNA analogs for studies such as DNA methylation and demethylation, and DNA damage and repair (Ali et al, 2006;Bley et al, 2011;Brickner et al, 2019;Calle-Fabregat et al, 2020;Gillingham & Sauter, 2017;Greenberg & Bourc'his, 2019;Michalak et al, 2019;Pande et al, 1999;Rhee & Pugh, 2011;Soll et al, 2017;Urbano et al, 2019).…”

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

“…The major chromatin changes in immune cells occur by DNA methylation and histone modifications, but also ATP‐dependent chromatin remodelling. The DNA methylation pattern primarily changes during haematopoiesis to alter gene expression patterns, 34 while acetylation and methylation of histones contribute to changes in gene expression also during differentiation and activation of immune cells 35‐37 . The epigenetic modification of chromatin is precisely regulated via histone‐modifying enzymes and chromatin remodelling enzymes acting on specific loci, resulting in specific changes in gene expression, chromatin organization and other DNA regulatory processes.…”