Epigenetic control during lymphoid development and immune responses: aberrant regulation, viruses, and cancer

Methylation of cytosines controls a number of biologic processes such as imprinting and X chromosomal inactivation. DNA hypermethylation is closely associated with transcriptional silencing, while DNA hypomethylation is associated with transcriptional activation. Hypoacetylation of histones leads to compact chromatin with reduced accessibility to the transcriptional machinery. Methyl-CpG binding proteins can recruit corepressors and histone deacetylases; thus, the interplay between these epigenetic mechanisms regulates gene activation. Methylation has been implicated as an important mechanism during immune development, controlling VDJ recombination, lineage-specific expression of cell surface antigens, and transcriptional regulation of cytokine genes during immune responses. Aberrations in epigenetic machinery, either by genetic mutations or by somatic changes such as viral infections, are associated with early alterations in chronic diseases such as immunodeficiency and cancer.