Researchers have developed CHARM, a sophisticated single-cell multi-omics sequencing method that simultaneously captures four distinct layers of cellular information: gene expression, chromatin accessibility, histone modifications, and three-dimensional genome architecture. By applying this tool to mouse embryonic stem cells and brain tissues, the study provides a comprehensive map of how the 3D epigenome dictates cell identity and function. The data reveals how epigenetic marks are restored during the cell cycle and how regulatory elements cluster in physical space to drive transcription. Furthermore, the authors utilized machine learning to identify thousands of enhancer-promoter linkages, offering new insights into the complex genetic regulation of the mouse cortex. This integrated approach overcomes previous technical limitations, providing a versatile platform for decoding the molecular landscapes of diverse cell types in complex biological systems.

References:

• Chen Y, Liu Z, Xu H, et al. Gene regulatory landscape dissected by single-cell four-omics sequencing[J]. Nature, 2026: 1-10.