PUBLICATION

Histone demethylases Kdm6ba and Kdm6bb redundantly promote cardiomyocyte proliferation during zebrafish heart ventricle maturation

Authors
Akerberg, A.A., Henner, A., Stewart, S., Stankunas, K.
ID
ZDB-PUB-170405-6
Date
2017
Source
Developmental Biology   426(1): 84-96 (Journal)
Registered Authors
Akerberg, Alex, Stankunas, Kryn, Stewart, Scott
Keywords
H3K27me3, Kdm6b, cardiogenesis, histone demethylase, trabeculation, ventricle
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Heart Ventricles/growth & development*
  • Histone Demethylases/genetics*
  • Histone Demethylases/metabolism
  • Histones/metabolism
  • Jumonji Domain-Containing Histone Demethylases/genetics*
  • Jumonji Domain-Containing Histone Demethylases/metabolism
  • Methylation
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Organogenesis/genetics*
  • Organogenesis/physiology
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
28372944 Full text @ Dev. Biol.
Abstract
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development. We pursued loss-of-function studies in zebrafish to define the conserved developmental roles of Kdm6b. kdm6ba and kdm6bb homozygous deficient zebrafish are each viable and fertile. However, loss of both kdm6ba and kdm6bb shows Kdm6b proteins share redundant and pleiotropic roles in organogenesis without impacting initial cell fate specification. In the developing heart, co-expressed Kdm6b proteins promote cardiomyocyte proliferation coupled with the initial stages of cardiac trabeculation. While newly formed trabecular cardiomyocytes display a striking transient decrease in bulk cellular H3K27me3 levels, this demethylation is independent of collective Kdm6b. Our results indicate a restricted and likely locus-specific role for Kdm6b demethylases during heart ventricle maturation rather than initial cardiogenesis.
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