Resolving Heart Regeneration by Replacement Histone Profiling.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Goldman, JA; Kuzu, G; Lee, N; Karasik, J; Gemberling, M; Foglia, MJ; Karra, R; Dickson, AL; Sun, F; Tolstorukov, MY; Poss, KD

Published Date

  • February 27, 2017

Published In

Volume / Issue

  • 40 / 4

Start / End Page

  • 392 - 404.e5

PubMed ID

  • 28245924

Pubmed Central ID

  • PMC5367476

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2017.01.013


  • eng

Conference Location

  • United States