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

Abstract

SUMMARYThis 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.

Integrative genomic and transcriptomic analysis for pinpointing recurrent alterations of plant homeodomain genes and their clinical significance in breast cancer

“…H3K4me3 is a histone mark associated with active transcription. PHD binding of H3K4me3 occurs through an aromatic cage, similar to those observed in chromodomain, PWWP (Pro-Trp-Trp-Pro), and Tudor domains [4, 5]. Of note, one tryptophan (Trp) residue in the second β-strand of canonical PHD is absolutely conserved; this Trp forms one of the walls of the aromatic cage for H3K4me3 binding [5].…”

Transcriptional Regulation by Trithorax-Group Proteins

“…5A). KIS-L contains two chromodomains ( protein motifs that bind certain methylated histones are covered in Cheng 2014 andPatel 2014) and is therefore more similar to Mi2 and other members of the CHD family of chromatin-remodeling factors. The large size of KIS-L ( 575 kDa) has made it difficult to analyze this protein biochemically.…”

Structural and Functional Coordination of DNA and Histone Methylation

“…The functional implications of the structural determination of enzymes in linking histone modifications to that of DNA in mammalian cells are also discussed. This article is complemented by subsequent articles discussing the structure and function of proteins that read DNA and histone methylation (Patel 2014), and previous articles discussing histone acetylation writers (HATs), histone deacetylation (HDAC) “eraser” enzymes, and readers of these epigenetic marks (Marmorstein and Zhou 2014; Seto and Yoshida 2014). …”