Epigenetic Regulation of Cytokine Gene Expression in T Lymphocytes

Abstract

The developmental program of T helper and regulatory T cell lineage commitment is governed by both genetic and epigenetic mechanisms. The principal events, signaling pathways and the lineage determining factors involved have been extensively studied in the past ten years. Recent studies have elucidated the important role of chromatin remodeling and epigenetic changes for proper regulation of gene expression of lineage-specific cytokines. These include DNA methylation and histone modifications in epigenomic reprogramming during T helper cell development and effector T cell functions. This review discusses the basic epigenetic mechanisms and the role of transcription factors for the differential cytokine gene regulation in the T helper lymphocyte subsets.

Epigenetic Control of Cytokine Gene Expression

“…It has been appreciated for nearly forty years that conversion of cytosine to 5-methylcytosine (m 5 C) in DNA is associated with control of gene expression (Holliday & Pugh, 1975; Riggs, 1975). CpG methylation has primarily been linked to transcriptional repression, and consistent with this observation, gene promoter regions in particular tend to be devoid of m 5 C (Bird, 2002; Bird, Taggart, Frommer, Miller, & Macleod, 1985; Gardiner-Garden & Frommer, 1987; Lee, Sahoo, & Im, 2009; Meissner et al, 2008; Vaissière et al, 2008). While 60–90% of CpG sites are methylated across the genome, in CG-rich sequences known as CpG islands, which are present upstream of about 40% of human genes, CpG sites are typically unmethylated (Bird, 2000; Meissner et al, 2008; Miranda & Jones, 2007; Lee, Sahoo, et al, 2009; Turek-Plewa & Jagodziński, 2005).…”

“…Notably, DNA methylation and demethylation at specific loci, and its linked impact upon the ability of transcriptional activators to bind to regulatory elements, is a key feature of T cell lineage commitment (Barnes, 2011; Lee, Sahoo, et al, 2009; Li, 2002). A second major mechanism of transcriptional repression by DNA methylation involves the recruitment of HDACs to gene promoters by methyl-CpG-binding proteins (MeCPs), including MeCP2 and MBD2 (Feng et al, 2001; Jones et al, 1998; Nan et al, 1998; Ng et al, 1999).…”

Initial Phase of Epigenetic Pathways in Carcinogenesis and Mutagenesis

“…Yang et al [6] showed that the action of mitogens on T-cells involves DNA methylation. In fact, epigenetic pathways may be involved in the expression of the mitogens themselves [7]. Warburton et al [8] reported that epigenetic pathways are involved in the action of EGF on embryo cells.…”

Promising Epigenetic Approaches Targeting TH17 in Autoimmune Diabetes among Chronic Hepatitis C Infection

“…All of them are associated with transcriptional regulation and determination of the cellular transcriptome, thereby contributing to cell function (Lee et al, 2009) as shown in figure 1.…”