PUBLICATION

Resolving Heart Regeneration by Replacement Histone Profiling

Authors
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.
ID
ZDB-PUB-170302-9
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
Datasets
GEO:GSE81865, GEO:GSE81863, GEO:GSE81862, 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
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes