Proximity labeling reveals a new in vivo network of interactors for the histone demethylase KDM5

Matanel Yheskel, Simone Sidoli, Julie Secombe

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Article number8
JournalEpigenetics and Chromatin
Issue number1
StatePublished - Dec 2023


  • Chromatin modifiers
  • Histone demethylase
  • Insulators
  • KDM5
  • Mass spectrometry
  • Proximity labeling
  • TurboID

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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