TRF2-mediated stabilization of hREST4 is critical for the differentiation and maintenance of neural progenitors.

摘要: Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex that known to bind and protect telomeric DNA, yet detection TRF2 in extra-telomeric regions chromosomes suggests other roles for besides telomere protection. Here, we demonstrate plays critical role antagonizing repressive function neuron-restrictive silencer factor, also as repressor element-1 silencing transcription (REST), during neural differentiation human embryonic stem cells (hESCs) by enhancing expression truncated REST splice isoform term REST4 (hREST4) due its similarity rodent REST4. We show specifically upregulated hESC concordantly with an increase hREST4 both proteins are highly expressed NPCs. Overexpression hESCs increases levels induces their differentiation, whereas knockdown NPCs reduces expression, hindering ability differentiate lineage. Concurrently, directly interacts C-terminal through core motif [F/Y]xL, protecting from ubiquitin-mediated proteasomal degradation consequently furthering induction. Thus, TRF2-mediated counterbalance between vital generation maintenance NPCs, suggesting important neurogenesis central nervous system. Stem Cells 2014;32:2111–2122