A Structural Perspective on Readout of Epigenetic Histone and DNA Methylation Marks

This article outlines the protein modules that target methylated lysine histone marks and 5mC DNA marks, and the molecular principles underlying recognition. The article focuses on the structural basis underlying readout of isolated marks by single reader molecules, as well as multivalent readout of multiple marks by linked reader cassettes at the histone tail and nucleosome level. Additional topics addressed include the role of histone mimics, cross talk between histone marks, technological developments at the genomewide level, advances using chemical biology approaches, the linkage between histone and DNA methylation, the role for regulatory lncRNAs, and the promise of chromatin-based therapeutic modalities. Outline 1 Introduction 2 Readout of Kme marks by PHD finger and BAH modules 3 Readout of methyllysine marks by single "Royal Family" modules 4 Readout of methyllysine marks by tandem Royal Family modules 5 Readout of methyllysine marks by expanded and paired modules 6 Readout of methylarginine marks by Tudor modules 7 Readout of unmodified lysine marks 8 Readout of unmodified arginine marks 9 Multivalent readout by linked binding modules at the peptide level 10 Multivalent readout by linked binding modules at the nucleosomal level 11 Alternate functional roles for PHD-bromo cassettes 12 Cross talk between histone marks 13 Histone mimics 14 Readout of fully methylated 5mCpG sites on DNA 15 Readout of hemimethylated 5mCpG sites on DNA 16 Perspectives and future challenges