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.
journal_name
Mol Celljournal_title
Molecular cellauthors
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 YE,Zhang D,Meng A,Shang Ydoi
10.1016/j.molcel.2014.06.006subject
Has Abstractpub_date
2014-08-07 00:00:00pages
482-94issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00488-2journal_volume
55pub_type
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