ZFIN ID: ZDB-PUB-170302-9
Resolving Heart Regeneration by Replacement Histone Profiling
Goldman, J.A., Kuzu, G., Lee, N., Karasik, J., Gemberling, M., Foglia, M.J., Karra, R., Dickson, A.L., Sun, F., Tolstorukov, M.Y., Poss, K.D.
Date: 2017
Source: Developmental Cell   40: 392-404.e5 (Journal)
Registered Authors: Dickson, Amy, Foglia, Matthew, Gemberling, Matt, Goldman, Joseph, Karra, Ravi, Lee, Nutishia, Poss, Kenneth D., Sun, Fei
Keywords: H3.3, cardiomyocyte, chromatin, enhancer, epigenetic, gene regulation, heart, histone, profiling, regeneration, zebrafish
Microarrays: GEO:GSE81862, GEO:GSE81863, GEO:GSE81865, GEO:GSE81893
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Binding Sites
  • Enhancer Elements, Genetic/genetics
  • Gene Expression Regulation, Developmental
  • Heart/physiology*
  • Histones/genetics
  • Histones/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Nucleotide Motifs/genetics
  • Regeneration/genetics
  • Regeneration/physiology*
  • Transcription Factors/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
PubMed: 28245924 Full text @ Dev. Cell
Chromatin regulation is a principal mechanism governing animal development, yet it is unclear to what extent structural changes in chromatin underlie tissue regeneration. Non-mammalian vertebrates such as zebrafish activate cardiomyocyte (CM) division after tissue damage to regenerate lost heart muscle. Here, we generated transgenic zebrafish expressing a biotinylatable H3.3 histone variant in CMs and derived cell-type-specific profiles of histone replacement. We identified an emerging program of putative enhancers that revise H3.3 occupancy during regeneration, overlaid upon a genome-wide reduction of H3.3 from promoters. In transgenic reporter lines, H3.3-enriched elements directed gene expression in subpopulations of CMs. Other elements increased H3.3 enrichment and displayed enhancer activity in settings of injury- and/or Neuregulin1-elicited CM proliferation. Dozens of consensus sequence motifs containing predicted transcription factor binding sites were enriched in genomic regions with regeneration-responsive H3.3 occupancy. Thus, cell-type-specific regulatory programs of tissue regeneration can be revealed by genome-wide H3.3 profiling.