In situ chromatin interactomics using a chemical bait and trap approach.

TitleIn situ chromatin interactomics using a chemical bait and trap approach.
Publication TypeJournal Article
Year of Publication2020
AuthorsBurton, AJ, Haugbro, M, Gates, LA, Bagert, JD, C Allis, D, Muir, TW
JournalNat Chem
Date Published2020 Jun
KeywordsChromatin, Epigenesis, Genetic, Histone Code, Histone Demethylases, Histones, Humans, Methyltransferases, Mutation, Neoplasms, Photoaffinity Labels, Protein Processing, Post-Translational, Proteomics

<p>Elucidating the physiological binding partners of histone post-translational modifications (hPTMs) is key to understanding fundamental epigenetic regulatory pathways. Determining such interactomes will enable the study of how perturbations of these interactions affect disease. Here we use a synthetic biology approach to set a series of hPTM-controlled photo-affinity traps in native chromatin. Using quantitative proteomics, the local interactomes of these chemically customized chromatin landscapes are determined. We show that the approach captures transiently interacting factors such as methyltransferases and demethylases, as well as previously reported and novel hPTM reader proteins. We also apply this in situ proteomics approach to a recently disclosed cancer-associated histone mutation, H3K4M, revealing a number of perturbed interactions with the mutated tail. Collectively our studies demonstrate that modifying and interrogating native chromatin with chemical precision is a powerful tool for exploring epigenetic regulation and dysregulation at the molecular level.</p>

Alternate JournalNat Chem
PubMed ID32472103
PubMed Central IDPMC7331920
Grant ListF32 GM123659 / GM / NIGMS NIH HHS / United States
P01 CA196539 / CA / NCI NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States