Scientists at St. Jude Children’s Research Hospital discovered how cells retain their memory of differentiation during mitosis. The research, published in Nature, reveals a previously unknown role for the SWI/SNF chromatin remodeling complex, which is mutated in approximately 20% of all cancers.

During differentiation, stem cells transform into specialized cell types with specific functions. When cells divide, they must retain their current differentiation state and properly transfer their identity to daughter cells. Chromatin plays a crucial role in this process, and the SWI/SNF complexes regulate gene expression by modifying chromatin architecture to control a cell’s identity during differentiation.

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The St. Jude team discovered that subunits of the SWI/SNF complexes act as “bookmarks” during mitosis, safeguarding cell identity during division. The study emphasized the importance of two core subunits, SMARCE1 and SMARCB1, in which loss or mutation of either of these subunits is also observed in various cancers, such as rhabdoid tumors.

Contrary to previous beliefs, the team found that SMARCE1 and SMARCB1 bind to mitotic DNA. This binding is essential for the proper reactivation of genes after mitosis. When SMARCE1 was removed during mitosis, gene expression was disrupted, the binding of other “bookmarks” to their targets was impaired, and abnormal neural differentiation occurred.

Senior author Charles W.M. Roberts, M.D., Ph.D., explains, “SMARCB1 would be bound in mitosis to bookmark the genes that should be turned on after the cell divides. But SMARCB1 is deleted in nearly all cases of a highly lethal type of cancer called rhabdoid tumors, preventing the activation of genes that help cells differentiate.”

These findings provide a new understanding of how cells retain their memory of differentiation during division. By identifying SWI/SNF subunits’ role as mitotic bookmarks, the study sheds light on the mechanisms behind cancer development and potential therapeutic targets for a wide range of cancers.