WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription

Ali, Radiya G., Bellchambers, Helen M., Warr, Nicholas, Ahmed, Jehangir N., Barratt, Kristen S., Neill, Kieran, Diamand, Koula E.M., and Arkell, Ruth M. (2021) WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription. Journal of Cell Science, 134 (9). jcs256792.

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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.

Item ID: 81345
Item Type: Article (Research - C1)
ISSN: 0021-9533
Copyright Information: © 2021. Published by The Company of Biologists Ltd
Date Deposited: 20 Mar 2024 03:36
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320801 Cell physiology @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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