PT  - JOURNAL ARTICLE
AU  - Matanel Yheskel
AU  - Simone Sidoli
AU  - Julie Secombe
TI  - Proximity labeling reveals a new <em>in vivo</em> network of interactors for the histone demethylase KDM5
AID  - 10.1101/2022.11.20.517232
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.20.517232
4099  - http://biorxiv.org/content/early/2022/11/20/2022.11.20.517232.short
4100  - http://biorxiv.org/content/early/2022/11/20/2022.11.20.517232.full
AB  - 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. Using Drosophila melanogaster, we enriched for biotinylated proteins from KDM5-TurboID-expressing adult heads, and generated a novel control for DNA-adjacent background in the form of dCas9:TurboID. We identified both known and novel candidate proteins, including members of the SWI/SNF and NURF chromatin remodeling complexes, the non-specific lethal (NSL) complex, Mediator, and several insulator proteins. 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.Competing Interest StatementThe authors have declared no competing interest.