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ENHANCER EPIGENETICS

Is H3K4me1 at enhancers correlative or causative?

Nature Genetics volume 50, pages 4–5 (2018)Cite this article

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H3K4me1 is enriched at active and primed enhancers. However, whether H3K4me1 controls or simply correlates with enhancer activity and function has remained unclear. Several recent reports, including two in Nature Genetics, provide major mechanistic and functional insights into the role of H3K4me1 at enhancers.

In the last few years, epigenomic strategies have shown that genomes are filled with thousands of regulatory elements, such as enhancers, that are essential for the establishment of cell-type-specific gene expression programs1. Moreover, the general interest in enhancers has also increased owing to accumulating evidence suggesting that the genetic or structural disruption of enhancer function represents a major cause of human disease2. One powerful strategy to globally identify enhancers and to infer their regulatory state (for example, active, primed or poised) is to use distinctive chromatin signatures based on the enrichment profiles of several histone modifications3,4,5. Among these histone modifications, H3K4me1 is certainly important. First, coupled to H3K4me3 depletion, the presence of H3K4me1 distinguishes enhancers from proximal promoters4. Furthermore, H3K4me1 marks active and primed enhancers, which can be distinguished on the basis of the presence and absence of H3K27ac, respectively3,5. Consequently, a myriad of H3K4me1 profiles have been generated in different cell types and organisms to generate comprehensive enhancer maps. However, whether H3K4me1 has a regulatory function within enhancers or is simply a useful mark to identify them remained unclear (Fig. 1). Recent publications from the Ren, Shilatifard and Wysocka laboratories now provide major insights into the role of H3K4me1 at enhancers, suggesting overall that H3K4me1 might fine-tune, rather than tightly control, enhancer activity and function6,7,8.

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Fig. 1: H3K4me1 at enhancers: a chicken or the egg problem?

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Authors and Affiliations

  1. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

    Alvaro Rada-Iglesias

  2. Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany

    Alvaro Rada-Iglesias

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  1. Alvaro Rada-Iglesias
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Correspondence to Alvaro Rada-Iglesias.

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Rada-Iglesias, A. Is H3K4me1 at enhancers correlative or causative?. Nat Genet 50, 4–5 (2018). https://doi.org/10.1038/s41588-017-0018-3

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