Distinct kinetic mechanisms of H3K4 methylation catalyzed by MLL3 and MLL4 core complexes.

ABSTRACT: The methyltransferases MLL3 and MLL4 primarily catalyze the monomethylation of histone H3 lysine 4 (H3K4) on enhancers to regulate cell-type-specific gene expression and cell fate transition. MLL3 and MLL4 share almost identical binding partners and biochemical activities, but perform specific and nonredundant functions. The features and functions that distinguish MLL3 and MLL4 remain elusive. Here, we characterize the kinetic mechanisms of MLL3 and MLL4 ternary complexes containing the catalytic SET domain from MLL3 or MLL4 (MLL3_SET or MLL4_SET), the SPRY domain of ASH2L (ASH2L_SPRY), and a short fragment of RBBP5 (RBBP5_AS-ABM) to search for possible explanations. Steady-state kinetic analyses and inhibition studies reveal that the MLL3 complex ca

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC8144669 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature