Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.

ABSTRACT: Heterozygous mutations in any of the six H3K4 methyltransferases (KMT2s) result in monogenic neurodevelopmental disorders, indicating non-redundant yet poorly understood roles of this enzyme family in neurodevelopment. However, the specific cellular role of KMT2 enzymes in the brain remains poorly understood, owing to the clear non-catalytic functions of each family member and the potential for functional redundancy in installing H3K4 methylation (H3K4me). Here, we identify an instructive role for H3K4me in controlling synapse function and a division of labor among the six KMT2 enzymes in regulating homeostatic synaptic scaling. Using RNAi screening, conditional genetics, small-molecule inhibitors, and transcriptional profiling, our data reveal that individual KMT2 enzymes have unique role

SUBMITTER: Tsukahara T 

PROVIDER: S-EPMC12289303 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature