PUBLICATION
Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome
- Authors
- Wu, T.F., Yao, Y.L., Lai, I.L., Lai, C.C., Lin, P.L., Yang, W.M.
- ID
- ZDB-PUB-150708-5
- Date
- 2015
- Source
- The Journal of biological chemistry 290(33): 20556-64 (Journal)
- Registered Authors
- Keywords
- PAX3, arginine methylation, chromosomes, homeobox, homeodomain, mitosis, mitotic chromosome, mutant, protein arginine N-methyltransferase 5 (PRMT5), transcription factor
- MeSH Terms
-
- Animals
- Arginine/metabolism*
- Chromosomes, Human*
- HEK293 Cells
- Humans
- Larva/metabolism
- Methylation
- Mitosis/genetics*
- Paired Box Transcription Factors/genetics*
- Protein-Arginine N-Methyltransferases/metabolism
- Waardenburg Syndrome/genetics*
- Zebrafish/growth & development
- PubMed
- 26149688 Full text @ J. Biol. Chem.
Citation
Wu, T.F., Yao, Y.L., Lai, I.L., Lai, C.C., Lin, P.L., Yang, W.M. (2015) Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome. The Journal of biological chemistry. 290(33):20556-64.
Abstract
PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain (HD). PAX3 WS mutants with mutations in HD lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3's loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping