Decoding the protein composition of whole nucleosomes with Nuc-MS

Luis F. Schachner, Kevin Jooß, Marc A. Morgan, Andrea Piunti, Matthew J. Meiners, Jared O. Kafader, Alexander S. Lee, Marta Iwanaszko, Marcus A. Cheek, Jonathan M. Burg, Sarah A. Howard, Michael-Christopher Keogh, Ali Shilatifard, Neil L. Kelleher

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Current proteomic approaches disassemble and digest nucleosome particles, blurring readouts of the ‘histone code’. To preserve nucleosome-level information, we developed Nuc-MS, which displays the landscape of histone variants and their post-translational modifications (PTMs) in a single mass spectrum. Combined with immunoprecipitation, Nuc-MS quantified nucleosome co-occupancy of histone H3.3 with variant H2A.Z (sixfold over bulk) and the co-occurrence of oncogenic H3.3K27M with euchromatic marks (for example, a >15-fold enrichment of dimethylated H3K79me2). Nuc-MS is highly concordant with chromatin immunoprecipitation-sequencing (ChIP-seq) and offers a new readout of nucleosome-level biology.
Original languageEnglish
Pages (from-to)303-308
JournalNature Methods
Volume18
Issue number3
DOIs
Publication statusPublished - 1 Mar 2021
Externally publishedYes

Funding

FundersFunder number
Howard Hughes Medical Institute59008810
National Institute on AgingRF1AG063903
NIH Office of the DirectorS10OD025194
National Cancer InstituteK99CA234434-01, R44CA212733, R44CA214076
National Institute of General Medical SciencesP41GM108569, T32GM105538, R44GM116584

    Fingerprint

    Dive into the research topics of 'Decoding the protein composition of whole nucleosomes with Nuc-MS'. Together they form a unique fingerprint.

    Cite this