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.

目前的蛋白质组学方法分解并消化核小体颗粒，模糊了“组蛋白密码”的读数。为了保留核小体水平的信息，我们开发了 Nuc-MS，它可以在单个质谱中显示组蛋白变体及其翻译后修饰 (PTM) 的情况。与免疫沉淀相结合，Nuc-MS 定量了组蛋白 H3.3 与变体 H2A.Z 的核小体共占用（体积的六倍）以及致癌 H3.3K27M 与常染色标记的共现（例如，>15 倍富集）二甲基化H3K79me2)。 Nuc-MS 与染色质免疫沉淀测序 (ChIP-seq) 高度一致，并提供核小体水平生物学的新读数。