Voigt et al. developed a mass-spectrometry-based method for studying the histone modifications of single nucleosomes. In various cell types, they found that modifications such as histone H3 lysine methylations occurred both asymmetrically and symmetrically (that is, they were present on either one or both copies of the histone family member in the nucleosomal octamer). These distinctions have biological relevance; for example, methylation of H3K27 by Polycomb-repressive complex 2 (PRC2) was inhibited only when both copies of histone H3 had either H3K4me3 or H3K36me3 modifications. Such symmetry considerations add another layer of complexity to the histone code.