Chemical tools for trapping histone modification enzymes on nucleosome substrates for structural studies
- 1Division of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599
- 2Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
- 3Department of Biochemistry and Biophysics, UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27599
Abstract
Histone post-translational modifications (PTMs) serve as gatekeepers for our genome through regulation of protein recruitment and modulation of chromatin structure. Dysregulation of the enzymes that add and remove histone PTMs is common in diverse disease states and histone modifying enzymes are emerging as important therapeutic targets. As such, it has been a priority to understand molecular mechanisms governing histone modifying enzyme function on physiologic nucleosome substrates. However, structural studies remain challenging due to the inherent low affinity and transient nature of many enzyme-nucleosome interactions. Over the last decade a growing number of chemical biology tools have been reported to trap histone modifying enzymes in action on nucleosomes for structural biology. We took this opportunity to review these strategies and highlight recent advances they have enabled in chromatin biology.
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BibTeX
@article{gordon2026chemical,
title = {{Chemical tools for trapping histone modification enzymes on nucleosome substrates for structural studies}},
author = {Jacob Gordon and Robert K. McGinty},
journal = {Current opinion in chemical biology},
year = {2026},
month = oct,
doi = {10.1016/j.cbpa.2026.102802},
url = {https://doi.org/10.1016/j.cbpa.2026.102802},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Chemical tools for trapping histone modification enzymes on nucleosome substrates for structural studies
AU - Jacob Gordon
AU - Robert K. McGinty
PY - 2026
DA - 2026/10/27
JO - Current opinion in chemical biology
DO - 10.1016/j.cbpa.2026.102802
UR - https://doi.org/10.1016/j.cbpa.2026.102802
AB - Histone post-translational modifications (PTMs) serve as gatekeepers for our genome through regulation of protein recruitment and modulation of chromatin structure. Dysregulation of the enzymes that add and remove histone PTMs is common in diverse disease states and histone modifying enzymes are emerging as important therapeutic targets. As such, it has been a priority to understand molecular mechanisms governing histone modifying enzyme function on physiologic nucleosome substrates. However, structural studies remain challenging due to the inherent low affinity and transient nature of many enzyme-nucleosome interactions. Over the last decade a growing number of chemical biology tools have been reported to trap histone modifying enzymes in action on nucleosomes for structural biology. We took this opportunity to review these strategies and highlight recent advances they have enabled in chromatin biology.
SN - 1367-5931
SN - 1879-0402
ER -