Your browser doesn't support javascript.
loading
Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior.
Guo, Jianhua; Zou, Zhongyu; Dou, Xiaoyang; Zhao, Xiang; Wang, Yimin; Wei, Liqiang; Pi, Yan; Wang, Yi; He, Chuan; Guo, Su.
Affiliation
  • Guo J; State Key Laboratory of Genetic Engineering, National Demonstration Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
  • Zou Z; Department of Chemistry and Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Dou X; Department of Chemistry and Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Zhao X; Department of Bioengineering and Therapeutic Sciences, Programs in Human Genetics and Biological Sciences, University of California, San Francisco, CA 94143, USA.
  • Wang Y; Department of Neurology, Children's Hospital of Fudan University, National Children's Medical Center, No. 399, Wanyuan Road, Minhang District, Shanghai, China.
  • Wei L; State Key Laboratory of Genetic Engineering, National Demonstration Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
  • Pi Y; Department of Bioengineering and Therapeutic Sciences, Programs in Human Genetics and Biological Sciences, University of California, San Francisco, CA 94143, USA.
  • Wang Y; State Key Laboratory of Genetic Engineering, National Demonstration Center for Experimental Biology Education, School of Life Sciences, Fudan University, Shanghai, China.
  • He C; Department of Bioengineering and Therapeutic Sciences, Programs in Human Genetics and Biological Sciences, University of California, San Francisco, CA 94143, USA.
  • Guo S; Department of Neurology, Children's Hospital of Fudan University, National Children's Medical Center, No. 399, Wanyuan Road, Minhang District, Shanghai, China.
Nucleic Acids Res ; 52(8): 4257-4275, 2024 May 08.
Article in En | MEDLINE | ID: mdl-38366571
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Zebrafish / Histones / Zebrafish Proteins / 5-Methylcytosine / Ubiquitination Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2024 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Zebrafish / Histones / Zebrafish Proteins / 5-Methylcytosine / Ubiquitination Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2024 Document type: Article Affiliation country: China