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

Cell Proliferation
Histone Demethylases/genetics*
Histone Demethylases/metabolism
Organogenesis/genetics*
Organogenesis/physiology
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism
Animals, Genetically Modified
Methylation
Zebrafish
Myocytes, Cardiac/cytology
Myocytes, Cardiac/metabolism*
Gene Knockout Techniques
Animals
Jumonji Domain-Containing Histone Demethylases/genetics*
Jumonji Domain-Containing Histone Demethylases/metabolism
Histones/metabolism
Gene Expression Regulation, Developmental
Heart Ventricles/growth & development*
Cell Differentiation/genetics

(all 20)

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.

Genes / Markers

Figures