Reader protein recognition of histone post-translational modifications: Role of aromatic interactions and cooperativity
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Updated: Oct 30, 2026

Histone Modification Screening using Liquid Chromatography, Trapped Ion Mobility Spectrometry, and Time-Of-Flight Mass Spectrometry
Published on: January 12, 2024
Christopher R Travis1, Jake R Wilkinson2, Marcey L Waters2
1Department of Chemistry, CB 3290, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Abstract:
Histone post-translational modifications (PTMs) mediate protein-protein interactions (PPIs) with reader proteins. These PPIs are key elements to epigenetic regulation of gene expression and have been linked to a wide range of cancers. However, inhibition of these interactions has proven challenging. Many of these PPIs are mediated by aromatic interactions with the PTM as well as interactions with the surrounding histone sequence. This review describes mechanistic studies of these binding interfaces and the role of cooperativity between recognition of the PTM and neighboring residues. These studies provide new insights that may help advance reader protein inhibitor development.
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