Creation of a Yeast Strain with Co-Translationally Acylated Nucleosomes

Structurally diverse acylations have been identified as post-translational modifications (PTMs) on histone lysine residues, but their functions and regulations remain largely unknown. Interestingly, in nature, a lysine acylation analog, pyrrolysine, is introduced as a co-translational modification (CTM) through genetic encoding. To explore this alternative life form, we created a model organism Saccharomyces cerevisiae containing site-specific lysine CTMs (acetyl-lysine, crotonyl-lysine, or another synthetic analog) at histone H3K56 using non-canonical amino acid mutagenesis to afford a chemically modified nucleosome in lieu of their own in vivo. We further demonstrated that acetylation of histone H3K56 partly tends to provide a more favorable chromatin environment for DNA repair in yeast compared to crotonylation and crosstalk with other PTMs differently. This study provides a potentially universal approach to decipher the consequences of different histone lysine PTMs in eukaryotes.

Automated summary

This study investigates the functions and regulations of structurally diverse acylations as post-translational modifications (PTMs) on histone lysine residues. It introduces the concept of a lysine acylation analog, pyrrolysine, as a co-translational modification (CTM) through genetic encoding. By creating a model organism Saccharomyces cerevisiae with site-specific lysine CTMs at histone H3K56, the study demonstrates that acetylation of histone H3K56 provides a more favorable chromatin environment for DNA repair compared to crotonylation and crosstalk with other PTMs differently. This research provides a potentially universal approach to understanding the consequences of different histone lysine PTMs in eukaryotes.