PUBLICATION

RNF4 regulates zebrafish granulopoiesis through the DNMT1-C/EBPα axis

Authors
Wang, L., Liu, X., Wang, H., Yuan, H., Chen, S., Chen, Z., de The, H., Zhou, J., Zhu, J.
ID
ZDB-PUB-180418-6
Date
2018
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   32(9): 4930-4940 (Journal)
Registered Authors
Chen, Zhu, Zhu, Jun
Keywords
STUbL, SUMOylation, myelopoiesis, neutrophil
MeSH Terms
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha/metabolism
  • DNA (Cytosine-5-)-Methyltransferase 1/genetics
  • DNA (Cytosine-5-)-Methyltransferase 1/metabolism*
  • DNA Repair/genetics
  • Gene Expression Regulation/genetics*
  • Hematopoiesis/genetics
  • Humans
  • Mutation/genetics*
  • Nuclear Proteins/genetics*
  • SUMO-1 Protein/genetics
  • SUMO-1 Protein/metabolism*
  • Sumoylation/genetics
  • Sumoylation/physiology
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
29634367 Full text @ FASEB J.
Abstract
RING finger protein 4 (RNF4) is a multifunctional small ubiquitin-related modifier (SUMO)-targeted ubiquitin E3 ligase (STUbL) ubiquitously expressed in all tissues, and which mainly participates in DNA repair and in chromatin and transcriptional regulation. Although RNF4 has been implicated in hematopoietic disorders, its ontogenic role during hematopoietic development remains undiscovered. We generated a zebrafish rnf4 knockout line by using transcription activator-like effector nucleases technology to address the impact of rnf4 during hematopoiesis. Rnf4-deficient zebrafish embryos exhibited sharply decreased neutrophils numbers during both primitive and definitive hematopoiesis. Mechanistic studies revealed that repression of the key granulocytic activator, CCAAT/enhancer-binding protein α ( c/ebpα), via promoter hypermethylation by SUMOylated DNA methyltransferase 1 (DNMT1) was the main cause of impaired granulopoiesis in rnf4-deficient zebrafish. In addition, for the first time, we identified DNMT1 as a potential new STUbL substrate of RNF4, with knockdown of dnmt1 largely restoring primitive and definitive granulopoiesis in rnf4-deficient zebrafish. Collectively, RNF4 is indispensable for zebrafish granulopoiesis through regulation of the DNMT1-C/EBPα functional axis.-Wang, L., Liu, X., Wang, H., Yuan, H., Chen, S., Chen, Z., de The, H., Zhou, J., Zhu, J. RNF4 regulates zebrafish granulopoiesis through the DNMT1-C/EBPα axis.
Genes / Markers
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes