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WNT responsive SUMOylation of ZIC5 promotes murine neural crest cell development via multiple effects on transcription

J Cell Sci. 2021-03; 
Radiya G Ali, Helen M Bellchambers, Nicholas Warr, Jehangir N Ahmed, Kristen S Barratt, Kieran Neill, Koula E M Diamand, Ruth M Arkell
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摘要

Zinc finger of the cerebellum (Zic) proteins act as classical transcription factors to promote transcription of the gene during neural crest cell specification. Additionally, they can act as co-factors that bind TCF molecules to repress WNT/β-catenin-dependent transcription without contacting DNA. Here, we show ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In a high WNT environment, a lysine within the highly conserved ZF-NC domain of ZIC5 is SUMOylated, which decreases formation of the TCF/ZIC co-repressor complex and shifts the balance towards transcription factor function. The modification is critical , as a ZIC5 SUMO-incompetent mouse strain exhibits neural crest spec... More

关键词

Co-factor, Foxd3, Mouse neural crest cell, Post-translational modification, TCF, Transcription factor