Local chromatin context informs transcriptional outcomes for the histone demethylase KDM5.

ABSTRACT:

Background

Lysine demethylase 5 (KDM5) family proteins are transcriptional regulators best known for demethylating the promoter-proximal histone mark H3K4me3. KDM5-mediated regulation of gene expression is crucial in the brain, with pathogenic variants in human KDM5 genes leading to intellectual disability (ID) disorders. Although the demethylase activity of KDM5 proteins is vital for brain function, non-enzymatic functions also contribute. How KDM5 uses distinct features to regulate transcription in a context-dependent manner remains largely uncharacterized.

Results

Using Drosophila, we demonstrate that a demethylase-dead Kdm5^JmjC* strain expands the distribution of promoter-proximal H3K4me3 in the brain, whereas Kdm5^L854F, which models a pathogenic ID

SUBMITTER: Yheskel M 

PROVIDER: S-EPMC12676786 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature