PUBLICATION

PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction

Authors
Peng, X., Feng, G., Zhang, Y., Sun, Y.
ID
ZDB-PUB-211116-10
Date
2021
Source
International Journal of Molecular Sciences   22(21): (Journal)
Registered Authors
Zhang, Yanyong
Keywords
PRC1, Rnf2, cardiac conduction system, cardiac contraction, sarcomere assembly
MeSH Terms
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism*
  • Ubiquitin-Protein Ligases/physiology
  • Sarcomeres/metabolism*
  • Sarcomeres/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology
  • Muscle Contraction*
  • Myocardium/metabolism*
  • Embryonic Development
  • Polycomb Repressive Complex 1/metabolism
  • Polycomb Repressive Complex 1/physiology
  • Heart/growth & development*
  • Heart/physiology
  • Loss of Function Mutation
  • Animals, Genetically Modified
  • Zebrafish/metabolism*
  • Zebrafish/physiology
  • Animals
(all 20)
PubMed
34768802 Full text @ Int. J. Mol. Sci.
Abstract
Cardiac development is a complex process that is strictly controlled by various factors, including PcG protein complexes. Several studies have reported the critical role of PRC2 in cardiogenesis. However, little is known about the regulation mechanism of PRC1 in embryonic heart development. To gain more insight into the mechanistic role of PRC1 in cardiogenesis, we generated a PRC1 loss-of-function zebrafish line by using the CRISPR/Cas9 system targeting rnf2, a gene encoding the core subunit shared by all PRC1 subfamilies. Our results revealed that Rnf2 is not involved in cardiomyocyte differentiation and heart tube formation, but that it is crucial to maintaining regular cardiac contraction. Further analysis suggested that Rnf2 loss-of-function disrupted cardiac sarcomere assembly through the ectopic activation of non-cardiac sarcomere genes in the developing heart. Meanwhile, Rnf2 deficiency disrupts the construction of the atrioventricular canal and the sinoatrial node by modulating the expression of bmp4 and other atrioventricular canal marker genes, leading to an impaired cardiac conduction system. The disorganized cardiac sarcomere and defective cardiac conduction system together contribute to defective cardiac contraction. Our results emphasize the critical role of PRC1 in the cardiac development.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
acta1af1Tg (AB)standard conditionsLong-pecRTPCR
acta1af1Tg (AB)standard conditionsPrim-5RTPCR
acta1af1Tg (AB)standard conditionsPrim-25RTPCR
acta1arnf2ihb806/ihb806; f1Tg (AB)standard conditionsLong-pecRTPCR
acta1arnf2ihb806/ihb806; f1Tg (AB)standard conditionsPrim-5RTPCR
acta1arnf2ihb806/ihb806; f1Tg (AB)standard conditionsPrim-25RTPCR
acta1bf1Tg (AB)standard conditionsLong-pecRTPCR
acta1bf1Tg (AB)standard conditionsPrim-5RTPCR
acta1bf1Tg (AB)standard conditionsPrim-25RTPCR
acta1brnf2ihb806/ihb806; f1Tg (AB)standard conditionsLong-pecRTPCR
1 - 10 of 108
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Phenotype
Fish Conditions Stage Phenotype Figure
rnf2ihb806/ihb806 (AB)standard conditions75%-epiboly
rnf2ihb806/ihb806 (AB)standard conditions75%-epiboly
rnf2ihb806/ihb806 (AB)standard conditions75%-epiboly
rnf2ihb806/ihb806 (AB)standard conditionsPrim-5
rnf2ihb806/ihb806 (AB)standard conditionsPrim-5
rnf2ihb806/ihb806 (AB)standard conditionsPrim-25
rnf2ihb806/ihb806 (AB)standard conditionsPrim-25
rnf2ihb806/ihb806 (AB)standard conditionsLong-pec
rnf2ihb806/ihb806 (AB)standard conditionsLong-pec
rnf2ihb806/ihb806 (AB)standard conditionsLong-pec
1 - 10 of 74
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f1TgTransgenic Insertion
    ihb806
      		Small Deletion
      ihb808
        		Small Deletion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        rnf2CRISPR1-rnf2CRISPR
        1 - 1 of 1
        Show
        Fish
        Fish
        AB
        f1Tg (AB)
        rnf2ihb806/ihb806 (AB)
        rnf2ihb806/ihb806; f1Tg (AB)
        rnf2ihb808/ihb808 (AB)
        1 - 5 of 5
        Show
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab3-rnf2polyclonal
          		IgGRabbit
          1 - 1 of 1
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          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
          Show
          Mapping
          No data available
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          Citation
          Peng, X., Feng, G., Zhang, Y., Sun, Y. (2021) PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction. International Journal of Molecular Sciences. 22(21):.