Abstract
Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.
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Change history
11 July 2018
In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since it inadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation of nucleosomes from HeLa cells had been used). A new Fig. 1b is provided in the Author Correction.
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Acknowledgements
Work in the R.S. laboratory is supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft (through SFB 746), Human Frontier Science Program, the EU (the Epigenome) and a European Research Council starting grant. We are grateful to T. Jenuwein (Max Planck Institute, Freiburg) for providing Suv39dn MEFs. We thank L. Tora for support. M.-E.T.-P. acknowledges funding from Avenir and PNRRE/INSERM.
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Daujat, S., Weiss, T., Mohn, F. et al. H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming. Nat Struct Mol Biol 16, 777–781 (2009). https://doi.org/10.1038/nsmb.1629
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DOI: https://doi.org/10.1038/nsmb.1629
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