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The 4D Nucleome (4DN) program, funded by the National Institutes of Health Common Fund, was established in 2015 to map the three-dimensional organization of the nucleus in space and time (the 4th dimension). In its first phase, the consortium focused on developing and benchmarking experimental and computational methods for measuring genome architecture. This effort generated a foundational resource of chromatin interaction data across key human cell types. The program’s second phase, beginning in 2021, shifted focus toward understanding chromatin dynamics and their functional implications for human health and disease. As the 4DN program approaches its conclusion in 2025, this collection highlights pivotal advances from its final five years published across Nature Portfolio.