Abstract
Histone post-translational modifications (PTMs) have been linked to a variety of biological processes and disease states, thus making their characterization a critical field of study. In the last 5 years, a number of novel sites and types of modifications have been discovered, greatly expanding the histone code. Mass spectrometric methods are essential for finding and validating histone PTMs. Additionally, novel proteomic, genomic and chemical biology tools have been developed to probe PTM function. In this snapshot review, proteomic tools for PTM identification and characterization will be discussed and an overview of PTMs found in the last 5 years will be provided.
Highlights
50 years ago Vincent Allfrey described histone acetylation [1]
While Post-translational modification (PTM) are found on all five histones, they commonly map to histone N-terminal tails [3]
Characterization of novel post-translational modifications As seen above, the discovery of a new modification raises a variety of questions, including: (1) is the modification evolutionarily conserved, (2) where in the genome is it localized [51], how abundant is it, (4) does it occur in the tails or globular domain of the histone, (5) what enzymes are responsible for acquisition/removal, (6) does it crosstalk with previously known modifications or histone variants, (7) does it antagonize other PTMs or abrogate binding of their reader proteins, and (8) what proteins bind or 'read' the modification? The answers to these questions lend insight into the biological function of the PTM
Summary
50 years ago Vincent Allfrey described histone acetylation [1]. Since research has been focused on identifying and mapping a growing list of histone posttranslational modifications (PTMs), including lysine acetylation, arginine and lysine methylation, phosphorylation, proline isomerization, ubiquitination (Ub), ADP ribosylation, arginine citrullination, SUMOylation, carbonylation and, with some controversy, biotinylation [2]. Competition of N-formylation with other modifications for lysine residues could be a way DNA oxidation resulting from cellular metabolism can impact PTM-mediated cellular processes [33]. Characterization of novel post-translational modifications As seen above, the discovery of a new modification raises a variety of questions, including: (1) is the modification evolutionarily conserved, (2) where in the genome is it localized [51], how abundant is it, (4) does it occur in the tails or globular domain of the histone, (5) what enzymes are responsible for acquisition/removal, (6) does it crosstalk with previously known modifications or histone variants, (7) does it antagonize other PTMs or abrogate binding of their reader proteins, and (8) what proteins bind or 'read' the modification? The analyses indicate that modifications on all four core histones can effect positively or negatively the modification levels on H3K56 and H3K79 [60]
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