Proximity Labeling Reveals a New in Vivo Network of Interactors for the Histone Demethylase KDM5

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2023 Feb 21

PMID 36803422

Authors

Matanel Yheskel

Simone Sidoli

Julie Secombe

Affiliations

Soon will be listed here.

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.

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References

Scandaglia M, Lopez-Atalaya J, Medrano-Fernandez A, Lopez-Cascales M, Del Blanco B, Lipinski M . Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons. Cell Rep. 2017; 21(1):47-59. PMC: 5679733. DOI: 10.1016/j.celrep.2017.09.014. View

Zamurrad S, Hatch H, Drelon C, Belalcazar H, Secombe J . A Drosophila Model of Intellectual Disability Caused by Mutations in the Histone Demethylase KDM5. Cell Rep. 2018; 22(9):2359-2369. PMC: 5854480. DOI: 10.1016/j.celrep.2018.02.018. View

Mittal P, Roberts C . The SWI/SNF complex in cancer - biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020; 17(7):435-448. PMC: 8723792. DOI: 10.1038/s41571-020-0357-3. View

Lee N, Zhang J, Klose R, Erdjument-Bromage H, Tempst P, Jones R . The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat Struct Mol Biol. 2007; 14(4):341-3. DOI: 10.1038/nsmb1216. View

Shokri L, Inukai S, Hafner A, Weinand K, Hens K, Vedenko A . A Comprehensive Drosophila melanogaster Transcription Factor Interactome. Cell Rep. 2019; 27(3):955-970.e7. PMC: 6485956. DOI: 10.1016/j.celrep.2019.03.071. View

Holowatyj A, Yang Z, Pile L . Histone lysine demethylases in Drosophila melanogaster. Fly (Austin). 2015; 9(1):36-44. PMC: 4594552. DOI: 10.1080/19336934.2015.1074787. View

Zhang B, Zhang Y, Liu J . Highly effective proximate labeling in Drosophila. G3 (Bethesda). 2021; 11(5). PMC: 8104946. DOI: 10.1093/g3journal/jkab077. View

Maharjan M, McKowen J, Hart C . Overlapping but Distinct Sequences Play Roles in the Insulator and Promoter Activities of the BEAF-Dependent scs' Insulator. Genetics. 2020; 215(4):1003-1012. PMC: 7404239. DOI: 10.1534/genetics.120.303344. View

Cao J, Liu Z, Cheung W, Zhao M, Chen S, Chan S . Histone demethylase RBP2 is critical for breast cancer progression and metastasis. Cell Rep. 2014; 6(5):868-77. PMC: 4014129. DOI: 10.1016/j.celrep.2014.02.004. View

10.

Harrington J, Wheway G, Willaime-Morawek S, Gibson J, Walters Z . Pathogenic KDM5B variants in the context of developmental disorders. Biochim Biophys Acta Gene Regul Mech. 2022; 1865(5):194848. DOI: 10.1016/j.bbagrm.2022.194848. View

11.

Horton J, Engstrom A, Zoeller E, Liu X, Shanks J, Zhang X . Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2015; 291(6):2631-46. PMC: 4742734. DOI: 10.1074/jbc.M115.698449. View

12.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

13.

Ramirez F, Ryan D, Gruning B, Bhardwaj V, Kilpert F, Richter A . deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016; 44(W1):W160-5. PMC: 4987876. DOI: 10.1093/nar/gkw257. View

14.

Ramirez F, Bhardwaj V, Arrigoni L, Lam K, Gruning B, Villaveces J . High-resolution TADs reveal DNA sequences underlying genome organization in flies. Nat Commun. 2018; 9(1):189. PMC: 5768762. DOI: 10.1038/s41467-017-02525-w. View

15.

Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann K, Speicher D . Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell. 2013; 23(6):811-25. PMC: 3810180. DOI: 10.1016/j.ccr.2013.05.003. View

16.

Kidder B, Hu G, Zhao K . KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation. Genome Biol. 2014; 15(2):R32. PMC: 4053761. DOI: 10.1186/gb-2014-15-2-r32. View

17.

Mannix K, Starble R, Kaufman R, Cooley L . Proximity labeling reveals novel interactomes in live tissue. Development. 2019; 146(14). PMC: 6679357. DOI: 10.1242/dev.176644. View

18.

Paroni G, Bolis M, Zanetti A, Ubezio P, Helin K, Staller P . HER2-positive breast-cancer cell lines are sensitive to KDM5 inhibition: definition of a gene-expression model for the selection of sensitive cases. Oncogene. 2018; 38(15):2675-2689. DOI: 10.1038/s41388-018-0620-6. View

19.

Chen X, Yin X, Li J, Wu Z, Qi Y, Wang X . Structures of the human Mediator and Mediator-bound preinitiation complex. Science. 2021; 372(6546). DOI: 10.1126/science.abg0635. View

20.

Vallianatos C, Farrehi C, Friez M, Burmeister M, Keegan C, Iwase S . Altered Gene-Regulatory Function of KDM5C by a Novel Mutation Associated With Autism and Intellectual Disability. Front Mol Neurosci. 2018; 11:104. PMC: 5893713. DOI: 10.3389/fnmol.2018.00104. View