| Literature DB >> 25018020 |
Xiao Han1, Bin Gui1, Cong Xiong2, Linnan Zhao3, Jing Liang1, Luyang Sun1, Xiaohan Yang1, Wenhua Yu1, Wenzhe Si1, Ruorong Yan1, Xia Yi1, Di Zhang1, Wanjin Li1, Lifang Li1, Jianguo Yang1, Yan Wang4, Yi Eve Sun5, Dai Zhang3, Anming Meng2, Yongfeng Shang6.
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.Entities:
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Year: 2014 PMID： 25018020 DOI： 10.1016/j.molcel.2014.06.006
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970