A study published in Science presents a single-cell atlas of DNA methylation and three-dimensional genome organization across the human body. Zhou and colleagues profiled 86,689 nuclei from 16 adult tissues, characterizing 35 major cell types and 206 subtypes. Their findings reveal extensive cell type–specific differences in methylation, chromatin loops, and long-range genome organization, while showing that these epigenomic features provide complementary information about cellular identity and differentiation. This resource may help researchers interpret how disease-associated genetic variants alter gene regulation in specific cell types. (https://www.science.org/doi/10.1126/science.adx0673)