PUBLICATION

Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior

Authors
Guo, J., Zou, Z., Dou, X., Zhao, X., Wang, Y., Wei, L., Pi, Y., Wang, Y., He, C., Guo, S.
ID
ZDB-PUB-240218-10
Date
2024
Source
Nucleic acids research   52(8): 4257-4275 (Journal)
Registered Authors
Guo, Su, He, Chuan
Keywords
none
Datasets
GEO:GSE225204, GEO:GSE222803
MeSH Terms
  • Animals
  • Epigenesis, Genetic
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Histones*/metabolism
  • DNA Methylation
  • Gene Expression Regulation, Developmental
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • 5-Methylcytosine*/metabolism
  • Ubiquitination*
  • Embryonic Development/genetics
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
(all 16)
PubMed
38366571 Full text @ Nucleic Acids Res.
Abstract
Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionarily conserved methyl-CpG-binding domain (MBD)-containing proteins are known as readers of DNA methylation. MBD5 is linked to multiple human diseases but its mechanism of action remains unclear. Here we report that the zebrafish Mbd5 does not bind to methylated DNA; but rather, it directly binds to 5-methylcytosine (m5C)-modified mRNAs and regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior. We further show that Mbd5 facilitates removal of the monoubiquitin mark at histone H2A-K119 through an interaction with the Polycomb repressive deubiquitinase (PR-DUB) complex in vivo. The direct target genes of Mbd5 are enriched with both RNA m5C and H2A-K119 ubiquitylation signals. Together, we propose that zebrafish MBD5 is an RNA m5C reader that potentially links RNA methylation to histone modification and in turn transcription regulation in vivo.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
mbd5CRISPR5-mbd5CRISPR
mbd5CRISPR6-mbd5CRISPR
mbd5CRISPR7-mbd5CRISPR
mbd5MO2-mbd5MRPHLNO
tp53MO4-tp53MRPHLNO
1 - 5 of 5
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Fish
No data available
Antibodies
Name Type Antigen Genes Isotypes Host Organism
Ab4-h2amonoclonal
    		IgGRabbit
    Ab32-gapdhmonoclonal
      		IgGRabbit
      Ab55-h3monoclonal
        		IgGRabbit
        1 - 3 of 3
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        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available
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        Citation
        Guo, J., Zou, Z., Dou, X., Zhao, X., Wang, Y., Wei, L., Pi, Y., Wang, Y., He, C., Guo, S. (2024) Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior. Nucleic acids research. 52(8):4257-4275.