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Flexible and site-specific manipulation of histones in live animals

Finkin-Groner, E.; Al-Kachak, A.; Agustinus, A. S.; Bastle, R.; Lepack, A.; Lyu, Y.; Maze, I.; David, Y.

2023-03-20 biochemistry
10.1101/2023.03.19.533378 bioRxiv
Show abstract

Recent advances in protein engineering have provided a wealth of methods that allow for the site-specific manipulation of proteins in vitro and in cells. However, the efforts to expand these toolkits for use in live animals has been limited. Here, we report a new method for the semi-synthesis of site-specifically modified and chemically defined proteins in live animals. Importantly, we illustrate the usefulness of this methodology in the context of a challenging, chromatin bound N-terminal histone tail within rodent postmitotic neurons located in ventral striatum (Nucleus Accumbens/NAc). This approach provides the field with a precise and broadly applicable methodology for manipulating histones in vivo, thereby serving as a unique template towards examining chromatin phenomena that may mediate transcriptomic and physiological plasticity within mammals.

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