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Epigenomics

Functional epigenomics: chromatin complexity untangled

Nature Structural & Molecular Biology (2023)Cite this article

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The development of an epigenetics-focused, CRISPR-based high-content functional genomics screening platform provides insight into chromatin regulation and uncovers a potential strategy to treat an aggressive type of leukemia.

An exciting area of functional genomics is the adaptation of complex biological readouts amenable to high-throughput screening1. Epigenetic regulation of chromatin biology is a multifactorial process with fundamental roles in human health and disease2,3. However, to date, a method to functionally investigate the gene networks regulating epigenetic mechanisms at chromatin using CRISPR-based screening technology has not been described. In their work, Gilan et al.4 develop a functional epigenomic platform termed ‘CRISPR–ChIP’ for identifying genes involved in determining a specific chromatin state and demonstrate in proof-of-concept experiments how this system can be used to uncover insights into the molecular pathways underpinning regulation of two key activating histone modifications (Fig. 1a).

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Fig. 1: CRISPR–ChIP functional genomics platform for analysis of epigenetic pathways regulating H3K4me3 and H3K79me2.

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Acknowledgements

This work was supported in part by grants from the US National Institutes of Health to O.G. (R35 GM139569 and R01 CA278940) and R.M. (T32 CA009302).

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  1. Department of Biology, Stanford University, Stanford, CA, USA

    Ricardo Mack & Or Gozani

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  1. Ricardo Mack
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  2. Or Gozani
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Correspondence to Or Gozani.

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Competing interests

O.G. is a scientific co-founder and stockholder of EpiCypher, Inc., K36 Therapeutics, Inc. and Alternative Bio, Inc.

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Mack, R., Gozani, O. Functional epigenomics: chromatin complexity untangled. Nat Struct Mol Biol (2023). https://doi.org/10.1038/s41594-023-01088-3

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