Abstract
Background: KDM5 family proteins are multi-domain regulators of transcription that when dysregulated contribute to cancer and intellectual disability. KDM5 proteins can regulate transcription through their histone demethylase activity in addition to demethylase-independent gene regulatory functions that remain less characterized. To expand our understanding of the mechanisms that contribute to KDM5-mediated transcription regulation, we used TurboID proximity labeling to identify KDM5-interacting proteins. Results: Using Drosophila melanogaster, we enriched for biotinylated proteins from KDM5-TurboID-expressing adult heads using a newly generated control for DNA-adjacent background in the form of dCas9:TurboID. Mass spectrometry analyses of biotinylated proteins identified both known and novel candidate KDM5 interactors, including members of the SWI/SNF and NURF chromatin remodeling complexes, the NSL complex, Mediator, and several insulator proteins. Conclusions: Combined, our data shed new light on potential demethylase-independent activities of KDM5. In the context of KDM5 dysregulation, these interactions may play key roles in the alteration of evolutionarily conserved transcriptional programs implicated in human disorders.
Original language | English (US) |
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Article number | 8 |
Journal | Epigenetics and Chromatin |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Keywords
- Chromatin modifiers
- Histone demethylase
- Insulators
- KDM5
- Mass spectrometry
- Proximity labeling
- TurboID
ASJC Scopus subject areas
- Molecular Biology
- Genetics