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Development (Cambridge, England)
02 15, 2022;149 (4):

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration.

Yingxi Cao, Yu Xia, Joseph J Balowski, Jianhong Ou, Lingyun Song, Alexias Safi, Timothy Curtis, Gregory E Crawford, Kenneth D Poss, Jingli Cao
Author Information
  1. Yingxi Cao: Cardiovascular Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, USA. ORCID
  2. Yu Xia: Cardiovascular Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, USA.
  3. Joseph J Balowski: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
  4. Jianhong Ou: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. ORCID
  5. Lingyun Song: Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA.
  6. Alexias Safi: Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA.
  7. Timothy Curtis: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
  8. Gregory E Crawford: Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA.
  9. Kenneth D Poss: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
  10. Jingli Cao: Cardiovascular Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, USA.
PMID: 35179181 DOI: 10.1242/dev.200133

Abstract

The epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identify tissue regeneration enhancer elements (TREEs) that control injury-induced epicardial gene expression during heart regeneration, we profiled transcriptomes and chromatin accessibility in epicardial cells purified from regenerating zebrafish hearts. We identified hundreds of candidate TREEs, which are defined by increased chromatin accessibility of non-coding elements near genes with increased expression during regeneration. Several of these candidate TREEs were incorporated into stable transgenic lines, with five out of six elements directing injury-induced epicardial expression but not ontogenetic epicardial expression in larval hearts. Whereas two independent TREEs linked to the gene gnai3 showed similar functional features of gene regulation in transgenic lines, two independent ncam1a-linked TREEs directed distinct spatiotemporal domains of epicardial gene expression. Thus, multiple TREEs linked to a regeneration gene can possess either matching or complementary regulatory controls. Our study provides a new resource and principles for understanding the regulation of epicardial genetic programs during heart regeneration. This article has an associated 'The people behind the papers' interview.

Keywords

ATAC-seq Enhancer Epicardium Heart regeneration TREE Zebrafish

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Grants

  1. R01 HL131319/NHLBI NIH HHS
  2. R35 HL150713/NHLBI NIH HHS
  3. 18CDA34110108/American Heart Association-American Stroke Association
  4. R01 HL155607/NHLBI NIH HHS

MeSH Term

Animals
Animals, Genetically Modified
Chromatin
Enhancer Elements, Genetic
GTP-Binding Protein alpha Subunits, Gi-Go
Gene Expression Regulation
Heart
Larva
Nerve Tissue Proteins
Neural Cell Adhesion Molecules
Pericardium
Regeneration
Zebrafish
Zebrafish Proteins

Chemicals

Chromatin
Nerve Tissue Proteins
Neural Cell Adhesion Molecules
Zebrafish Proteins
ncam1a protein, zebrafish
GTP-Binding Protein alpha Subunits, Gi-Go
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

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