ZFIN ID: ZDB-PUB-200229-13
Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility
Lee, H.J., Hou, Y., Chen, Y., Dailey, Z.Z., Riddihough, A., Jang, H.S., Wang, T., Johnson, S.L.
Date: 2020
Source: Genome biology   21: 52 (Journal)
Registered Authors: Chen, Yujie, Johnson, Stephen L., Lee, Hyung Joo, Wang, Ting
Keywords: Chromatin accessibility, DNA methylation, Fate restriction, Fin, Osteoblast, Regeneration, Zebrafish
Microarrays: GEO:GSE126700, GEO:GSE126701, GEO:GSE126702, GEO:GSE126703
MeSH Terms:
  • Animal Fins/cytology
  • Animal Fins/metabolism*
  • Animal Fins/physiology
  • Animals
  • Cell Lineage*
  • Chromatin Assembly and Disassembly
  • DNA Methylation*
  • Epigenome*
  • Gene Regulatory Networks
  • Osteoblasts/cytology
  • Osteoblasts/metabolism
  • Regeneration*
  • Zebrafish
PubMed: 32106888 Full text @ Genome Biol.
FIGURES
ABSTRACT
Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage. Epigenetic changes that are associated with lineage restriction during regeneration remain underexplored.
We produce epigenome maps, including DNA methylation and chromatin accessibility, as well as transcriptomes, of osteoblasts and other cells in uninjured and regenerating fins. This effort reveals regeneration as a process of highly dynamic and orchestrated transcriptomic and chromatin accessibility changes, coupled with stably maintained lineage-specific DNA methylation. The epigenetic signatures also reveal many novel regeneration-specific enhancers, which are experimentally validated. Regulatory networks important for regeneration are constructed through integrative analysis of the epigenome map, and a knockout of a predicted upstream regulator disrupts normal regeneration, validating our prediction.
Our study shows that lineage-specific DNA methylation signatures are stably maintained during regeneration, and regeneration enhancers are preset as hypomethylated before injury. In contrast, chromatin accessibility is dynamically changed during regeneration. Many enhancers driving regeneration gene expression as well as upstream regulators of regeneration are identified and validated through integrative epigenome analysis.
ADDITIONAL INFORMATION