ZFIN ID: ZDB-PUB-170214-313
Destabilizing LSD1 by Jade-2 promotes neurogenesis: an antibraking system in neural development
Han, X., Gui, B., Xiong, C., Zhao, L., Liang, J., Sun, L., Yang, X., Yu, W., Si, W., Yan, R., Yi, X., Zhang, D., Li, W., Li, L., Yang, J., Wang, Y., Sun, Y.E., Zhang, D., Meng, A., Shang, Y.
Date: 2014
Source: Molecular Cell   55: 482-94 (Journal)
Registered Authors: Meng, Anming, Xiong, Cong, Yan, Ruorong
Keywords: none
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Embryonic Stem Cells/metabolism*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental
  • HeLa Cells
  • Histone Demethylases/genetics
  • Histone Demethylases/metabolism*
  • Humans
  • Mice
  • Neuroblastoma/metabolism*
  • Neuroblastoma/physiopathology
  • Neurogenesis*
  • Oxidoreductases, N-Demethylating/genetics
  • Oxidoreductases, N-Demethylating/metabolism
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 25018020 Full text @ Mol. Cell
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ABSTRACT
Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryonic stem cell (ESC) differentiation toward neural lineage. We showed that the destabilization of LSD1 occurs posttranscriptionally via the ubiquitin-proteasome pathway by an E3 ubiquitin ligase, Jade-2. We demonstrated that Jade-2 is a major LSD1 negative regulator during neurogenesis in vitro and in vivo in both mouse developing cerebral cortices and zebra fish embryos. Apparently, Jade-2-mediated degradation of LSD1 acts as an antibraking system and serves as a quick adaptive mechanism for re-establishing epigenetic landscape without more laborious transcriptional regulations. As a potential anticancer strategy, Jade-2-mediated LSD1 degradation could potentially be used in neuroblastoma cells to induce differentiation toward postmitotic neurons.
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