WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription
| Autor: | Nicholas Warr, Helen M. Bellchambers, Ruth M. Arkell, Jehangir N. Ahmed, Kristen S. Barratt, Radiya G. Ali, Koula E. M. Diamand, Kieran Neill |
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| Rok vydání: | 2021 |
| Předmět: |
Zinc finger
0303 health sciences animal structures 030302 biochemistry & molecular biology SUMO protein Wnt signaling pathway Sumoylation Neural crest Cell Differentiation Cell Biology Biology Cell biology Mice 03 medical and health sciences Neural Crest Transcription (biology) embryonic structures Animals TCF Transcription Factors FOXD3 Neural plate Transcription factor beta Catenin Transcription Factors 030304 developmental biology |
| Zdroj: | Journal of Cell Science. 134 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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