DOT1L and PRC1.1: A chromatin tug-of-war with therapeutic implications
A new study in *Nature Cell Biology* reveals a critical antagonistic relationship between the histone methyltransferase DOT1L and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) in regulating transcriptional memory. The research demonstrates that PRC1.1-mediated gene silencing is actively counteracted by DOT1L activity. This dynamic balance is not just a fundamental mechanism of epigenetic control but is also identified as a key determinant for the efficacy of targeted therapies, specifically Menin and DOT1L inhibitors, in treating mixed-lineage leukaemia (MLL).
Why it might matter to you: This work directly connects core epigenetic mechanisms—chromatin remodeling and transcriptional regulation—to a tangible therapeutic outcome in cancer. For professionals focused on gene expression regulation, epigenetics, and cancer cell biology, it provides a mechanistic blueprint for how disrupting specific chromatin modifiers can alter cell fate. Understanding this DOT1L-PRC1.1 axis could inform the development of more precise combination therapies and help predict or overcome resistance in leukaemia and potentially other cancers driven by similar epigenetic dysregulation.
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