Breaking the histone code with quantitative mass spectrometry

Abstract

Histone post-translational modifications (PTMs) comprise one of the most intricate nuclear signaling networks that govern gene expression in a long-term and dynamic fashion. These PTMs are considered to be ‘epigenetic’ or heritable from one cell generation to the next and help establish genomic expression patterns. While much of the analyses of histones have historically been performed using site-specific antibodies, these methods are replete with technical obstacles (i.e., cross-reactivity and epitope occlusion). Mass spectrometry-based proteomics has begun to play a significant role in the interrogation of histone PTMs, revealing many new aspects of these modifications that cannot be easily determined with standard biological approaches. Here, we review the accomplishments of mass spectrometry in the histone field, and outline the future roadblocks that must be overcome for mass spectrometry-based proteomics to become the method of choice for chromatin biologists.

EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra*

“…Moreover, histone PTMs cross-talk in a synergistic manner to fine-tune gene expression (5). Therefore, quantification of histone PTMs has become a high priority to investigate cell regulation and epigenetics (6).…”

Human Adipocytes : Proteomic Approaches

“…Strahl and Allis suggested that a "histone code" could be read by regulatory proteins and complexes [217] and many have studied the code since then [170,171,[218][219][220][221][222][223][224][225][226]. Strahl an Allis also speculated that histone PTMs could influence the modification status of other sites on the same histone or in the same nucleosome by attracting or blocking specific enzymes and it did not take long until this was shown -H2BK123-ubiquitination is for example necessary for H3K4-methylation [227] and blocking H3K14-acetylation by mutation will prevent trimethylation of H3K4 [228].…”

Initial characterization of histone H3 serine 10 O-acetylation

“…9 Among others, new sites of acetylation, methylation, O-GlcNAcylation, crotonylation, propionylation, arginine citrullination, butyrylation, proline isomerization, malonylation, succinylation, formylation, and ADP-ribosylation have been detected and studied in a wide range of species and biological processes. [10][11][12][13][14][15][16] Serine acetylation was first reported as a chemical antagonist to phosphorylationmediated signaling pathways in eukaryotic cells, catalyzed by the Yersinia bacterial virulence factor, YopJ.…”