Decoding the Protein Composition of Whole Nucleosomes with Nuc-MS
L. F. Schachner, K. Jooss, M. A. Morgan, A. Piunti, M. J. Meiners, A. Lee, J. O. Kafader, M. Iwanaszko, M. A. Cheek, J. M. Burg, S. A. Howard, M.-C. Keogh, A. Shilatifard, N. L. Kelleher
Abstract
Nuc-MS characterizes histone modifications and variants directly from intact endogenous nucleosomes. Preserving whole nucleosome particles enables precise interrogation of their protein content, as for H3.3-containing nucleosomes which had 6-fold co-enrichment of variant H2A.Z over bulk chromatin. Nuc-MS, validated by ChIP-seq, showed co-occurrence of oncogenic H3.3K27M with euchromatic marks (e.g., H4K16ac and >15-fold enrichment of H3K79me2). By capturing the entire epigenetic landscape, Nuc-MS provides a new, quantitative readout of nucleosome-level biology.
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