Chromatin as a three-dimensional memory machine

Epigenetic memory-the stable inheritance of a cellular state over cell generations-has long been associated with chromatin modifications. But individual modifications are very dynamic. How can they carry information across cell generations? Recent theoretical work suggests the answer might lie, in part, in the three-dimensional organization of the genome. Cooperation between marks brought together by genome folding can correct epigenetic errors, making stable memory units out of unstable marks. If marks direct the phase separation of chromatin, the resulting bidirectional coupling between marks and structure provides a mechanism for many of these units to operate independently along the genome. Models of bidirectional coupling have helped identify elements, such as formation of a dense compartment, 3D mark spreading, and limited enzyme, which may be key to stable epigenetic memory. An analogy between these 3D models and a classic model of associative memory hints at a way chromatin could perform sophisticated information processing.