The MLL/KMT2 family enzymes are frequently mutated in human cancers and congenital diseases. They deposit the majority of histone 3 lysine 4 (H3K4) mono-, di-, or tri-methylation in mammals and are tightly associated with gene activation. Structural and biochemical studies in recent years provide in-depth understanding of how the MLL1 and homologous yeast SET1 complexes interact with the nucleosome core particle (NCP) and how their activities for H3K4 methylation are regulated by the conserved core components. Here, we will discuss the recent single molecule cryo-EM studies on the MLL1 and ySET1 complexes bound on the NCP. These studies highlight the dynamic regulation of the MLL/SET1 family lysine methyltransferases with unique features as compared with other histone lysine methyltransferases. These studies provide insights for loci-specific regulation of H3K4 methylation states in cells. The mechanistic studies on the MLL1 complex have already led to the development of the MLL1 inhibitors that show efficacy in acute leukemia and metastatic breast cancers. Future studies on the MLL/SET1 family enzymes will continue to bring to light potential therapeutic opportunities.
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Review Article| January 25 2023
Structural insights on the KMT2–NCP interaction
1Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, U.S.A.
2Department of Medicine, the Jane Ann Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California, Los Angeles, U.S.A.
Correspondence: Yali Dou (email@example.com)
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Zi Yang, Robert Zepeda, Yali Dou; Structural insights on the KMT2–NCP interaction. Biochem Soc Trans 27 February 2023; 51 (1): 427–434. doi: https://doi.org/10.1042/BST20221155
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