Exploration into the MLL4/WRAD Enzyme-Substrate Network: Systematic In Vitro Identification of CFP1 as a Potential Non-Histone Substrate of the MLL4 Lysine Methyltransferase.

ABSTRACT: Lysine methylation is a critical post-translational modification catalyzed by lysine methyltransferases (KMTs), originally characterized in the regulation of histones. However, the breadth of non-histone targets remains largely unexplored. Here, we used a systematic peptide array-based approach to define a substrate preference motif for the SET-domain-containing KMT MLL4 (KMT2D), a member of the COMPASS complex and a known H3K4 methyltransferase. Using this motif, we identified CXXC finger protein 1 (CFP1), a core component of Setd1A/B complexes, as a putative MLL4 substrate. In vitro methyltransferase assays confirmed robust methylation of CFP1 by an MLL4-WRAD complex. Surprisingly, while initial predictions implicated K328, array-based methylation profiling revealed multiple lysine resid

SUBMITTER: Boulter M 

PROVIDER: S-EPMC12551112 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature