title: Correlation between Shh expression and DNA methylation status of the limb-specific Shh enhancer region during limb regeneration in amphibians.
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.
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Nayuta
authors.initials: N
authors.lastname: Yakushiji
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Satoh
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sagai
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Hisato
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ide
authors.forename: Koji
authors.initials: K
authors.lastname: Tamura
mesh_terms: D024506:5' Flanking Region; D000663:Amphibians / Q000196:embryology*; D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D005121:Extremities / Q000196:embryology / Q000502:physiology*; D005123:Eye / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D012038:Regeneration; D017422:Sequence Analysis, DNA; D014982:Xenopus laevis
chemical_list: D053823:Hedgehog Proteins