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

Yheskel, M.; Sidoli, S.; Secombe, J.

doi:10.1101/2022.11.20.517232

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bioRxiv · 10.1101/2022.11.20.517232

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

Yheskel, M.·Sidoli, S.·Secombe, J.

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Abstract

BackgroundKDM5 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. ResultsUsing 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. ConclusionsCombined, 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.

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Yheskel, M., Sidoli, S., Secombe, J.. 2022-11-20. Proximity labeling reveals a new in vivo network of interactors for the histone demethylase KDM5. https://doi.org/10.1101/2022.11.20.517232

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