AI Article Synopsis
- Site-selective conjugation chemistry has been effective in creating uniform ubiquitinated histones, and a new method using CAET allows for the stable formation of ubiquitin chains.
- This strategy has been successfully applied to synthesize both single and dual-monoubiquitinated histones.
- These synthetic histones facilitate the study of DNMT1 binding to ubiquitinated nucleosomes, advancing the research in epigenetics.
Article Abstract
Site-selective conjugation chemistry has proven effective to synthesize homogenously ubiquitinated histones. Recently, a powerful strategy using 2-((2-chloroethyl) amino) ethane-1-thiol (CAET) as a bifunctional handle was developed to generate chemically stable ubiquitin chains without racemization and homodimerization. Herein, we extend this strategy to the expedient synthesis of ubiquitinated histones, exemplifying its utility to not only synthesize single-monoubiquitinated histones, but dual-monoubiquitinated histones as well. The synthetic histones enabled us to evaluate the binding of DNMT1 to ubiquitinated nucleosomes and map the hotspots of this interaction. Our work highlights the potential of modern chemical protein synthesis to synthesize ubiquitinated histones for epigenetic studies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231317 | PMC |
| http://dx.doi.org/10.1039/d3sc00332a | DOI Listing |
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