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EPIGENOMICS

Histone gene editing probes functions of H3K27 modifications in mammals

Nature Genetics volume 54, pages 746–747 (2022)Cite this article

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A new study employs CRISPR–Cas9-based base editing for simultaneous mutagenesis of all copies of histone H3 genes in mammals, highlighting the functional importance of H3K27me3 for Polycomb-mediated gene silencing and the dispensability of H3K27ac in transcriptional activation.

Since the discovery of acetylated and methylated histones1, it has become clear that a complex language of histone post-translational modifications is associated with processes that act on chromatin, such as transcription2. In particular, histone tails support extensive chemical modifications, whose nature and functions are still object of intense investigation3. Despite vast amounts of epigenomic data correlating different modification patterns to distinct transcriptional states3, proofs of their causal roles in gene expression remain scarce in mammals. This is likely because each canonical histone is encoded by multiple genes (≥12) distributed across different chromosomes4, making traditional mutagenesis approaches based on individual gene targeting prohibitively difficult. In this issue of Nature Genetics, Sankar et al5. embark on a remarkable histone gene editing journey to determine the role of chemical modifications of lysine 27 on histone H3 (H3K27) in the regulation of transcription.

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Fig. 1: Functional investigation of H3K27 by massive parallel histone mutagenesis.

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Authors and Affiliations

  1. Epigenetics Institute, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Alessandro Scacchetti & Roberto Bonasio

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  1. Alessandro Scacchetti
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  2. Roberto Bonasio
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Correspondence to Roberto Bonasio.

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The authors declare no competing interests.

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Scacchetti, A., Bonasio, R. Histone gene editing probes functions of H3K27 modifications in mammals. Nat Genet 54, 746–747 (2022). https://doi.org/10.1038/s41588-022-01096-x

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