title: Resolving Heart Regeneration by Replacement Histone Profiling.
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.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Joseph Aaron
authors.initials: JA
authors.lastname: Goldman
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Guray
authors.initials: G
authors.lastname: Kuzu
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Nutishia
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Karasik
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gemberling
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Foglia
authors.affiliation: Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Karra
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Dickson
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: tolstorukov@molbio.mgh.harvard.edu.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tolstorukov
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA. Electronic address: kenneth.poss@duke.edu.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Poss
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D059372:Nucleotide Motifs / Q000235:genetics; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D006657:Histones; D014157:Transcription Factors
keywords: H3.3; cardiomyocyte; chromatin; enhancer; epigenetic; gene regulation; heart; histone; profiling; regeneration; zebrafish