Correlation between Shh expression and DNA methylation status of the limb-specific Shh enhancer region during limb regeneration in amphibians

Nayuta Yakushiji, Makoto Suzuki, Akira Satoh, Tomoko Sagai, Toshihiko Shiroishi, Hisato Kobayashi, Hiroyuki Sasaki, Hiroyuki Ide, Koji Tamura

Research output: Contribution to journalArticle

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Abstract

The Xenopus adult limb has very limited regeneration ability, and only a simple cartilaginous spike structure without digits is formed after limb amputation. We found that expression of Shh and its downstream genes is absent from the regenerating blastema of the Xenopus froglet limb. Moreover, we found that a limb enhancer region of the Shh gene is highly methylated in the froglet, although the sequence is hypomethylated in the Xenopus tadpole, which has complete limb regeneration ability. These findings, together with the fact that the promoter region of Shh is hardly methylated in Xenopus, suggest that regenerative failure (deficiency in repatterning) in the Xenopus adult limb is associated with methylation status of the enhancer region of Shh and that a target-specific epigenetic regulation is involved in gene re-activation for repatterning during the Xenopus limb regeneration process. Because the methylation level of the enhancer region was low in other amphibians that have Shh expression in the blastemas, a low methylation status may be the basic condition under which transcriptional regulation of Shh expression can progress during the limb regeneration process. These findings provide the first evidence for a relationship between epigenetic regulation and pattern formation during organ regeneration in vertebrates.

Original languageEnglish
Pages (from-to)171-182
Number of pages12
JournalDevelopmental Biology
Volume312
Issue number1
DOIs
Publication statusPublished - Dec 1 2007
Externally publishedYes

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Amphibians
DNA Methylation
Regeneration
Extremities
Xenopus
Methylation
Epigenomics
Amputation
Genetic Promoter Regions
Transcriptional Activation
Genes
Larva
Vertebrates

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Correlation between Shh expression and DNA methylation status of the limb-specific Shh enhancer region during limb regeneration in amphibians. / Yakushiji, Nayuta; Suzuki, Makoto; Satoh, Akira; Sagai, Tomoko; Shiroishi, Toshihiko; Kobayashi, Hisato; Sasaki, Hiroyuki; Ide, Hiroyuki; Tamura, Koji.

In: Developmental Biology, Vol. 312, No. 1, 01.12.2007, p. 171-182.

Research output: Contribution to journalArticle

Yakushiji, Nayuta ; Suzuki, Makoto ; Satoh, Akira ; Sagai, Tomoko ; Shiroishi, Toshihiko ; Kobayashi, Hisato ; Sasaki, Hiroyuki ; Ide, Hiroyuki ; Tamura, Koji. / Correlation between Shh expression and DNA methylation status of the limb-specific Shh enhancer region during limb regeneration in amphibians. In: Developmental Biology. 2007 ; Vol. 312, No. 1. pp. 171-182.
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