This study uses a multidimensional proteomics strategy to systematically examine the interaction of around 2,000 nuclear proteins with 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 driving protein recruitment or exclusion, the authors show how chromatin states are decoded by chromatin readers. They find that nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. The authors also develop an online resource, the Modification Atlas of Regulation by Chromatin States (MARCS), which provides in-depth analysis tools to engage with their results and advance the discovery of fundamental principles of genome regulation by chromatin states. The study bridges the gap between chromatin states and chromatin readers, offering insights into how complex combinatorial modification patterns underlying chromatin states are interpreted by chromatin readers.This study uses a multidimensional proteomics strategy to systematically examine the interaction of around 2,000 nuclear proteins with 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 driving protein recruitment or exclusion, the authors show how chromatin states are decoded by chromatin readers. They find that nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. The authors also develop an online resource, the Modification Atlas of Regulation by Chromatin States (MARCS), which provides in-depth analysis tools to engage with their results and advance the discovery of fundamental principles of genome regulation by chromatin states. The study bridges the gap between chromatin states and chromatin readers, offering insights into how complex combinatorial modification patterns underlying chromatin states are interpreted by chromatin readers.