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

14 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 (US)
Pages (from-to)271-282
Number of pages12
JournalDevelopmental Biology
Volume406
Issue number2
DOIs
StatePublished - Oct 15 2015

Fingerprint

Limb Buds
Xenopus
Epigenomics
Histone Code
Regeneration
Extremities
Histones
Lysine
Chromatin
Transcription Factors
Developmental Genes
Gene Expression
Chromatin Immunoprecipitation
Transcription Initiation Site
Amphibians
Morphogenesis
Genome

Keywords

  • Cellular memory
  • Epigenetic modification
  • Histone
  • Limb regeneration

Cite this

Hayashi, S., Kawaguchi, A., Uchiyama, I., Kawasumi-Kita, A., Kobayashi, T., Nishide, H., ... 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

Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration. / Hayashi, Shinichi; Kawaguchi, Akane; Uchiyama, Ikuo; Kawasumi-Kita, Aiko; Kobayashi, Takuya; Nishide, Hiroyo; Tsutsumi, Rio; Tsuru, Kazuhiko; Inoue, Takeshi; Ogino, Hajime; Agata, Kiyokazu; Tamura, Koji; Yokoyama, Hitoshi.

In: Developmental Biology, Vol. 406, No. 2, 15.10.2015, p. 271-282.

Research output: Contribution to journalArticle

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, vol. 406, no. 2, pp. 271-282. https://doi.org/10.1016/j.ydbio.2015.08.013
Hayashi S, Kawaguchi A, Uchiyama I, Kawasumi-Kita A, Kobayashi T, Nishide H et al. Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration. Developmental Biology. 2015 Oct 15;406(2):271-282. https://doi.org/10.1016/j.ydbio.2015.08.013
Hayashi, Shinichi ; Kawaguchi, Akane ; Uchiyama, Ikuo ; Kawasumi-Kita, Aiko ; Kobayashi, Takuya ; Nishide, Hiroyo ; Tsutsumi, Rio ; Tsuru, Kazuhiko ; Inoue, Takeshi ; Ogino, Hajime ; Agata, Kiyokazu ; Tamura, Koji ; Yokoyama, Hitoshi. / Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration. In: Developmental Biology. 2015 ; Vol. 406, No. 2. pp. 271-282.
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