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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 (US)
Pages (from-to)303-308
Number of pages6
JournalNature Methods
Issue number3
StatePublished - Mar 2021

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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