Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.14.16.2 (
tyrosine hydroxylase
)
14,760
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Epigenetic modifications play an important role in neural development. Trimethylated histone H3 at lysine 27 (H3K27me3) is a repressive epigenetic marker that mediates tissue development. In this study, we demonstrate that H3K27me3 and histone methyl transferase Ezh2 regulated the development of dopaminergic (DA) neurons in vitro and in vivo. We found that H3K27me3 increased during differentiation of ventral midbrain-derived neural stem cells (VM-NSCs). However,
histone demethylase
selective inhibitor GSK-J1 increased H3K27me3 level and decreased the expression of
tyrosine hydroxylase
. Treated with Ezh2-selective inhibitor EPZ005687 repressed the trimethylation of H3K27 and enhanced differentiation of DA neurons in VM-NSCs cultures. Furthermore, Ezh2 inhibition promoted the expression of DA neurons developmental-related factors by modifying H3K27 trimethylation on the relevant promoter regions. Moreover, the effect of Ezh2 inhibition-mediated DA neurons differentiation was blocked by the expression of shRNA specific for
Nurr1
. In vivo, Ezh2 decreased and resulted in a reduction of H3K27me3 in developing midbrain. Deletion of
Ezh2
by RNA interference approach promoted differentiation of DA neurons during midbrain development. Overexpression of
Ezh2
enhanced cell self-renewal and did not affect differentiation of DA neurons.
...
PMID:Inhibition of Ezh2 In Vitro and the Decline of
Ezh2
in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3. 3088 11
