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

Autor: Ali RG; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Bellchambers HM; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Warr N; Early Development, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK., Ahmed JN; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Barratt KS; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Neill K; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Diamand KEM; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia., Arkell RM; Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.; Early Development, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK.
Jazyk: angličtina
Zdroj: Journal of cell science [J Cell Sci] 2021 May 01; Vol. 134 (9). Date of Electronic Publication: 2021 May 17.
DOI: 10.1242/jcs.256792
Abstrakt: 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.
Competing Interests: Competing interests The authors declare no competing or financial interests.
(© 2021. Published by The Company of Biologists Ltd.)
Databáze: MEDLINE
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