Histone arginine methylation

Abstract

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code.

Figure 1. Types and sites of histone tail arginine methylation

(A) Arginine residues in the tails of histones can be monomethylarginines (MMA), asymmetric dimethylarginines (ADMA), and symmetric dimethylarginines (SDMA). The MMA form of arginine is generally regarded as an intermediate on its way to the dimethylated state and is not depicted here. (B) The known sites of histone H3, H4, and H2A arginine dimethylation are shown. Red denotes transcriptional repressor activity and green denotes transcriptional activator activity.

Figure 2. Mechanisms by which histone tail arginine methylation regulates transcription

(A) The symmetrical dimethylation of H3R2 blocks the binding of H3K4me3 effector molecules. In addition, the H3R2me2a mark prevents methylation of H3K4me3 by MLL1. (B) The H4R3me2s mark may function as a docking site for the PHD finger of the de novo DNA methyltransferase DNMT3A, thereby linking PRMT5 activity to stable and heritable DNA methylation. (C) The activation marks deposed by PRMT1 (H4R3me2a) and CARM1 (H3R17me2a) can be “read” by the tudor domain of TDRD3. TDRD3 itself functions as a coactivator, in some manner relaying the intent of these two PRMTs.