Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration

Shinichi Hayashi, Akane Kawaguchi, Ikuo Uchiyama, Aiko Kawasumi-Kita, Takuya Kobayashi, Hiroyo Nishide, Rio Tsutsumi, Kazuhiko Tsuru, Takeshi Inoue, Hajime Ogino, Kiyokazu Agata, Koji Tamura, Hitoshi Yokoyama

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Many amphibians can regenerate limbs, even in adulthood. If a limb is amputated, the stump generates a blastema that makes a complete, new limb in a process similar to developmental morphogenesis. The blastema is thought to inherit its limb-patterning properties from cells in the stump, and it retains the information despite changes in morphology, gene expression, and differentiation states required by limb regeneration. We hypothesized that these cellular properties are maintained as epigenetic memory through histone modifications. To test this hypothesis, we analyzed genome-wide histone modifications in Xenopus limb bud regeneration. The trimethylation of histone H3 at lysine 4 (H3K4me3) is closely related to an open chromatin structure that allows transcription factors access to genes, whereas the trimethylation of histone H3 at lysine 27 (H3K27me3) is related to a closed chromatin state that blocks the access of transcription factors. We compared these two modification profiles by high-throughput sequencing of samples prepared from the intact limb bud and the regenerative blastema by chromatin immunoprecipitation. For many developmental genes, histone modifications at the transcription start site were the same in the limb bud and the blastema, were stable during regeneration, and corresponded well to limb properties. These results support our hypothesis that histone modifications function as a heritable cellular memory to maintain limb cell properties, despite dynamic changes in gene expression during limb bud regeneration in Xenopus.

    Original languageEnglish
    Pages (from-to)271-282
    Number of pages12
    JournalDevelopmental Biology
    Volume406
    Issue number2
    DOIs
    Publication statusPublished - 2015 Oct 15

    Keywords

    • Cellular memory
    • Epigenetic modification
    • Histone
    • Limb regeneration

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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  • Cite this

    Hayashi, S., Kawaguchi, A., Uchiyama, I., Kawasumi-Kita, A., Kobayashi, T., Nishide, H., Tsutsumi, R., Tsuru, K., Inoue, T., Ogino, H., Agata, K., Tamura, K., & Yokoyama, H. (2015). Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration. Developmental Biology, 406(2), 271-282. https://doi.org/10.1016/j.ydbio.2015.08.013