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

Epigenetics & Chromatin

Research

Simone Sidoli¹  Matanel Yheskel²  Julie Secombe³ 

[1] Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA;Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA;

关键词: KDM5;    Histone demethylase;    TurboID;    Proximity labeling;    Mass spectrometry;    Chromatin modifiers;    Insulators;   

DOI  :  10.1186/s13072-023-00481-y

 received in 2022-12-07, accepted in 2023-02-03,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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