The role of protein deimination in epigenetics

Accumulating evidence suggests that epigenetic factors exemplified by histone posttranslational modification (PTM) cooperate with DNA sequence to control a diverse range of biological processes, including cell differentiation and reprogramming, organism development, and tissue homeostasis. Protein deimination of nucleosomal histones is a relatively less-characterized form of histone PTM. However, it appears to play a unique and incompletely understood role in epigenetics. At a molecular level, histone deimination directly antagonizes arginine methylation on histone tails, thereby interfering with the transcriptional consequences of such an effect. In addition, deimination can also affect the activity of important histone-modifying enzymes, such as the acetyl transferase p300, consequently amplifying the transcriptional outputs. In physiological or pathological conditions, histone deimination mediates chromatin decondensation and elicits cell-specific innate immune response in neutrophils; increased histone deimination has been observed in the normal-appearing white matter of multiple sclerosis (MS) patients. In this chapter, we first review the concepts in epigenetics and then discuss the roles that protein deimination play in human health and disease.