This study decodes chromatin states by profiling the interactions of nuclear proteins with modified dinucleosomes. Using a multidimensional proteomics approach, researchers systematically examined the binding of approximately 2,000 nuclear proteins to over 80 modified dinucleosomes representing promoter, enhancer, and heterochromatin states. By deconvoluting complex nucleosome-binding profiles into networks of co-regulated proteins and distinct nucleosomal features, the study reveals how chromatin states are interpreted by chromatin readers. The findings show that different chromatin features elicit distinct binding responses, with many proteins recognizing multiple features. Nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. The online resource MARCS provides tools for analyzing these results and advancing the understanding of genome regulation by chromatin states. The study highlights that chromatin states are defined by combinations of histone modifications, histone variants, and linker DNA. These combinations form the basis for defining chromatin states, which are used to annotate functional regions in the genome. Chromatin regulators often contain multiple modification-binding domains, indicating that recognizing multiple modifications is a key function of many nuclear proteins. However, few factors recognize multiple modifications, making the interpretation of complex modification patterns largely unclear. The researchers used SILAC nucleosome affinity purification (SNAP) to profile the interactomes of chromatin modifications in the nucleosomal context. They assembled nucleosomes from biotinylated DNA and histone octamers containing site-specifically modified histones. These nucleosomes were used in forward and reverse SILAC nucleosome pull-down experiments to identify proteins that bind to different chromatin states. The results show that chromatin readers respond to different modification states in distinct ways, with some proteins showing strong recruitment or exclusion based on specific modifications. The study also reveals that modifications and linkers act independently in recruiting proteins to chromatin. The INO80 chromatin remodeling complex, for example, shows binding to nucleosomes with specific modification signatures. The findings underscore the importance of chromatin modifications and linker DNA in regulating protein binding to chromatin. The online resource MARCS provides a platform for further exploration of these findings and their implications for understanding genome regulation by chromatin states.This study decodes chromatin states by profiling the interactions of nuclear proteins with modified dinucleosomes. Using a multidimensional proteomics approach, researchers systematically examined the binding of approximately 2,000 nuclear proteins to over 80 modified dinucleosomes representing promoter, enhancer, and heterochromatin states. By deconvoluting complex nucleosome-binding profiles into networks of co-regulated proteins and distinct nucleosomal features, the study reveals how chromatin states are interpreted by chromatin readers. The findings show that different chromatin features elicit distinct binding responses, with many proteins recognizing multiple features. Nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. The online resource MARCS provides tools for analyzing these results and advancing the understanding of genome regulation by chromatin states. The study highlights that chromatin states are defined by combinations of histone modifications, histone variants, and linker DNA. These combinations form the basis for defining chromatin states, which are used to annotate functional regions in the genome. Chromatin regulators often contain multiple modification-binding domains, indicating that recognizing multiple modifications is a key function of many nuclear proteins. However, few factors recognize multiple modifications, making the interpretation of complex modification patterns largely unclear. The researchers used SILAC nucleosome affinity purification (SNAP) to profile the interactomes of chromatin modifications in the nucleosomal context. They assembled nucleosomes from biotinylated DNA and histone octamers containing site-specifically modified histones. These nucleosomes were used in forward and reverse SILAC nucleosome pull-down experiments to identify proteins that bind to different chromatin states. The results show that chromatin readers respond to different modification states in distinct ways, with some proteins showing strong recruitment or exclusion based on specific modifications. The study also reveals that modifications and linkers act independently in recruiting proteins to chromatin. The INO80 chromatin remodeling complex, for example, shows binding to nucleosomes with specific modification signatures. The findings underscore the importance of chromatin modifications and linker DNA in regulating protein binding to chromatin. The online resource MARCS provides a platform for further exploration of these findings and their implications for understanding genome regulation by chromatin states.