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EPIGENETIC REGULATION

Heads or tails: histone tail clipping regulates macrophage activity

Nature Immunology volume 22, pages 678–680 (2021)Cite this article

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Chromatin undergoes extensive reprogramming during immune cell differentiation. Histone clipping, an underexplored epigenetic mechanism, ensures precise macrophage development and function and is now found to be dysregulated in autoinflammatory disease.

The ENCODE project (https://www.encodeproject.org/) is putting great effort into systematically mapping the human epigenetic regulatory landscape by characterizing histone marks, chromatin accessibility and 3D chromatin interactions, along with many other regulatory layers in numerous models and cell types. However, histone clipping is not included in this project and, in general, this type of epigenetic regulation is not a major research focus for the community. Histone clipping has been described in several species and processes such as yeast sporulation3, in the homeostasis of mouse intestinal villi4 and in the in vitro differentiation of human stem cells5. However, high throughput and quantitative detection of dozens of histone marks as well as histone clipping activity is challenging, especially in clinical samples. To overcome this difficulty, some of the authors previously developed a mass cytometry–based platform, epigenetic landscape profiling using cytometry by time-of-flight (EpiTOF)6, which relies on antibodies labelled with lanthanide to detect up to 35 different proteins in one experiment. This technology can be used to measure global levels of histone marks and histone tail clipping at the single-cell level. In this previous study, EpiTOF was applied to human peripheral blood mononuclear cells. Unexpectedly, a previously unexplored enrichment of histone H3 clipping was identified in human monocytes. This finding generated many questions and initiated the current study.

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Fig. 1: The dynamics of histone H3 tail clipping are important in the epigenetic regulation of monocyte-to-macrophage differentiation.

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Authors and Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Bjørt K. Kragesteen & Ido Amit

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  1. Bjørt K. Kragesteen
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  2. Ido Amit
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Correspondence to Bjørt K. Kragesteen or Ido Amit.

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Kragesteen, B.K., Amit, I. Heads or tails: histone tail clipping regulates macrophage activity. Nat Immunol 22, 678–680 (2021). https://doi.org/10.1038/s41590-021-00941-1

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