H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration

Research output: Contribution to journalArticle

Authors

  • Raz Ben-Yair
  • Vincent L. Butty
  • Michele Busby
  • Yutong Qiu
  • Stuart S. Levine
  • Alon Goren
  • Laurie A. Boyer
  • C. Geoffrey Burns
  • Caroline E. Burns

External Institution(s)

  • Harvard University
  • Massachusetts Institute of Technology
  • Broad Institute
  • University of California at San Diego

Details

Original languageEnglish (US)
Article numberdev178632
JournalDevelopment (Cambridge)
Volume146
Issue number19
StatusPublished - Jan 1 2019
Peer-reviewedYes

Abstract

Deciphering the genetic and epigenetic regulation of cardiomyocyte proliferation in organisms that are capable of robust cardiac renewal, such as zebrafish, represents an attractive inroad towards regenerating the human heart. Using integrated high-throughput transcriptional and chromatin analyses, we have identified a strong association between H3K27me3 deposition and reduced sarcomere and cytoskeletal gene expression in proliferative cardiomyocytes following cardiac injury in zebrafish. To move beyond an association, we generated an inducible transgenic strain expressing a mutant version of histone 3, H3.3K27M, that inhibits H3K27me3 catalysis in cardiomyocytes during the regenerative window. Hearts comprising H3.3K27M-expressing cardiomyocytes fail to regenerate, with wound edge cells showing heightened expression of structural genes and prominent sarcomeres. Although cell cycle re-entry was unperturbed, cytokinesis and wound invasion were significantly compromised. Collectively, our study identifies H3K27me3-mediated silencing of structural genes as requisite for zebrafish heart regeneration and suggests that repression of similar structural components in the border zone of an infarcted human heart might improve its regenerative capacity.

    Research areas

  • Cardiomyocyte, Cardiovascular, Chromatin, Epigenetic, H3K27me3, Heart regeneration, Proliferation, Zebrafish

Citation formats

APA

Ben-Yair, R., Butty, V. L., Busby, M., Qiu, Y., Levine, S. S., Goren, A., ... Burns, C. E. (2019). H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration. Development (Cambridge), 146(19), [dev178632]. https://doi.org/10.1242/dev.178632

Harvard

Ben-Yair, R, Butty, VL, Busby, M, Qiu, Y, Levine, SS, Goren, A, Boyer, LA, Geoffrey Burns, C & Burns, CE 2019, 'H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration', Development (Cambridge), vol. 146, no. 19, dev178632. https://doi.org/10.1242/dev.178632