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:GSE81893, GEO:GSE81862, GEO:GSE81865, GEO:GSE81863
- 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
Citation
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. (2017) Resolving Heart Regeneration by Replacement Histone Profiling. Developmental Cell. 40:392-404.e5.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping