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WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription.
- Source :
- TextilWirtschaft Online; Feb2022, p1-13, 13p, 1 Diagram, 4 Graphs
- Publication Year :
- 2022
-
Abstract
- Zinc finger of the cerebellum (Zic) proteins act as classic transcription factors to promote transcription of the Foxd3 gene during neural crest cell specification. Additionally, they can act as co-factors that bind proteins from the T-cell factor/lymphoid enhancing factor (TCF/LEF) family (TCFs) to repress WNT-β-catenin-dependent transcription without contacting DNA. Here, we show that ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In the presence of high canonical WNT activity, a lysine residue within the highly conserved zinc finger N-terminally conserved (ZF-NC) domain of ZIC5 is SUMOylated, which reduces formation of the ZIC-TCF co-repressor complex and shifts the balance towards transcription factor function. The modification is crucial in vivo, as a ZIC5 SUMO- incompetent mouse strain exhibits neural crest specification defects. This work reveals the function of the ZF-NC domain within ZIC, provides in vivo validation of target protein SUMOylation and demonstrates that WNT-β-catenin signalling directs transcription at non-TCF DNA-binding sites. Furthermore, it can explain how WNT signals convert a broad region of Zic ectodermal expression into a restricted region of neural crest cell specification. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- Database :
- Complementary Index
- Journal :
- TextilWirtschaft Online
- Publication Type :
- Periodical
- Accession number :
- 158948976
- Full Text :
- https://doi.org/10.1242/jcs.256792