Mass Spectrometry Based Proteomics for Interrogating the Histone Code

Peter      A. DiMaggio; Benjamin      A. Garcia

doi:10.2174/157016410792928189

Abstract

Biological research in recent years has been expedited by the advent of mass spectrometry-based proteomics. In the area of chromatin research, mass spectrometry has emerged as an important platform for characterizing the specific locations and types of post-translational modifications (PTMs) present on histone proteins. Substantial evidence supports the claim that chromatin structure is modulated by the “Histone Code” hypothesis, which states that specific posttranslational modifications (PTMs) of the histone proteins on the nucleosomes drive the formation of euchromatin (i.e., open and transcriptionally active chromatin) and heterochromatin (i.e., compact and transcriptionally repressed chromatin) by signaling and interacting with the appropriate transcriptional and chromatin remodeling machinery. Thus, the ability to accurately discover, identify, and quantify these modified forms is of immense value to the field. This article reviews the various mass spectrometric methods that have recently been developed for the study of histone variants and their posttranslational modifications.

Keywords: Histone proteins, post-translational modifications, mass spectrometry, Proteomics, Histone Code, Chromatin research, Post-translational modifications(PTMs), Chromatin remodeling machinery, Pre-initiation complex, Higher-order chromatin structure, histone H1, Modifying enzymes, Writers, Erasers, Specific modification site, Antibody-based methods, Electron capture dissociation (ECD), Electron transfer dissociation (ETD), Histone analysis, SDS-PAGE purification, MS-based proteomics, Co-elute, iTRAQ, Metabolic Labelling, Label-free