CRISPR–ChIP reveals selective regulation of H3K79me2 by Menin in MLL leukemia

O Gilan; L Talarmain; CC Bell; D Neville; K Knezevic; DT Ferguson; M Boudes; YC Chan; C Davidovich; EYN Lam; MA Dawson

Journal article

CRISPR–ChIP reveals selective regulation of H3K79me2 by Menin in MLL leukemia

O Gilan, L Talarmain, CC Bell, D Neville, K Knezevic, DT Ferguson, M Boudes, YC Chan, C Davidovich, EYN Lam, MA Dawson

Nature Structural and Molecular Biology | NATURE PORTFOLIO | Published : 2023

DOI: 10.1038/s41594-023-01087-4

Abstract

Chromatin regulation involves the selective recruitment of chromatin factors to facilitate DNA repair, replication and transcription. Here we demonstrate the utility of coupling unbiased functional genomics with chromatin immunoprecipitation (CRISPR–ChIP) to identify the factors associated with active chromatin modifications in mammalian cells. Specifically, an integrated reporter containing a cis-regulatory element of interest and a single guide RNA provide a chromatinized template for a direct readout for regulators of histone modifications associated with actively transcribed genes such as H3K4me3 and H3K79me2. With CRISPR–ChIP, we identify all the nonredundant COMPASS complex members req..

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University of Melbourne Researchers

Enid Lam Author

Mark Dawson Author

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Awarded by Monash University

Funding Acknowledgements

We thank the Flow Cytometry facility and Molecular Genomics Core at the Peter MacCallum Cancer Centre and the ARAFlowcore Flow facility at the Australian Centre for Blood Diseases, Monash University. We thank the following funders for fellowship, scholarship and grant support: VCA Mid-Career Research Fellowship (O.G.); Cancer Council Victoria Sir Edward Dunlop Research Fellowship, NHMRC Investigator Grant #1196749 and Howard Hughes Medical Institute International Research Scholarship #55008729 (M.A.D.); and NHMRC Project Grants #1146192 (O.G.), #1085015 / #1106444 (M.A.D.) and #1128984 (M.A.D.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.