Readers of histone modifications

Abstract

Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks. Accumulating evidence suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted.

Figure 1

Readers for acetylated lysines (AcK). Protein domains are illustrated in surface representations of electrostatic potential and histone peptides are depicted in stick structure or cartoons with target lysines labeled in green. (A) Recognition of AcK by the bromo domains of Rsc4 (PDB 2R10). H3K14ac (from 2R0Y) is superimposed on 2R10 using DaliLite. (B) Structure of the bromo domain BD1 of BRDT bound to H4K5acK8ac (PDB 2WP2).

Figure 2

Readers for methylated lysines. Unless specified otherwise, color coding is similar to Figure 1 except that flanking arginines were labeled in purple. (A) Recognition of H3K4me3 by TAF3-PHD (PDB 2K17). (B) Recognition of H3K4me3 by the double-Tudor domain of JMJD2A (PDB 2GFA). (C) L3MBTL1 MBT bound to H4K20me2 (PDB 2PQW). (D) Comparison of binding surfaces from different MeK readers. Lysines are labeled in brown and pocket-forming residues are labeled in green (PDB 2PUY, 2G6Q, 2K17, 2F6J and 2K3Y). (E) Recognition of H3K4me0 by BHC80 PHD (PDB 2PUY). (F) Recognition H3K36me3 by the PWWP domain of Brpf1 (PDB 2X4X).

Figure 3

Recognition of methyl-lysines by the WD40 domain of EED. (A) Sequence of histone peptides. (B) Superposition of the binding of histone peptides to EED using DaliLite (PDB 3K27, 3JZG, 3IIY and 3JPX). (C) Superposition of the apo-EED (yellow) and EED bound to K9me3 (black) (PDB 3K27 and 3JZN).

Figure 4

Readers for phosphorylated serines. (A) The BRCT domain of MDC1 binds to γH2AX (PDB 2AZM). (B) Recognition of H3K9acS10ph by14-3-3 (PDB 2C1J).

Figure 5

Structure of K79me nucleosomes. Histone H3 is labeled in yellow (PDB 3C1C).

Figure 6

Models for the functional outcomes of reading modified histones.