PUBLICATION

Loss of the Polycomb group protein Rnf2 results in derepression of tbx-transcription factors and defects in embryonic and cardiac development

Authors
Chrispijn, N.D., Elurbe, D.M., Mickoleit, M., Aben, M., de Bakker, D.E.M., Andralojc, K.M., Huisken, J., Bakkers, J., Kamminga, L.M.
ID
ZDB-PUB-190315-4
Date
2019
Source
Scientific Reports   9: 4327 (Journal)
Registered Authors
Aben, Marco, Andralojc, Karolina, Bakkers, Jeroen, Chrispijn, Naomi, Huisken, Jan, Kamminga, Leonie, Mickoleit, Michaela
Keywords
none
Datasets
GEO:GSE114038
MeSH Terms
  • Animals
  • Embryonic Development/genetics*
  • Heart/embryology*
  • Mutation
  • T-Box Domain Proteins/metabolism*
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/physiology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
30867528 Full text @ Sci. Rep.
Abstract
The Polycomb group (PcG) protein family is a well-known group of epigenetic modifiers. We used zebrafish to investigate the role of Rnf2, the enzymatic subunit of PRC1. We found a positive correlation between loss of Rnf2 and upregulation of genes, especially of those whose promoter is normally bound by Rnf2. The heart of rnf2 mutants shows a tubular shaped morphology and to further understand the underlying mechanism, we studied gene expression of single wildtype and rnf2 mutant hearts. We detected the most pronounced differences at 3 dpf, including upregulation of heart transcription factors, such as tbx2a, tbx2b, and tbx3a. These tbx genes were decorated by broad PcG domains in wildtype whole embryo lysates. Chamber specific genes such as vmhc, myh6, and nppa showed downregulation in rnf2 mutant hearts. The marker of the working myocard, nppa, is negatively regulated by Tbx2 and Tbx3. Based on our findings and literature we postulate that loss of Rnf2-mediated repression results in upregulation and ectopic expression of tbx2/3, whose expression is normally restricted to the cardiac conductive system. This could lead to repression of chamber specific gene expression, a misbalance in cardiac cell types, and thereby to cardiac defects observed in rnf2 mutants.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes