Nuclear S-nitrosylation impacts tissue regeneration in zebrafish

Gianfranco Matrone, Sung Yun Jung, Jong Min Choi, Antrix Jain, Hon Chiu Eastwood Leung, Kimal Rajapakshe, Cristian Coarfa, Julie Rodor, Martin A. Denvir, Andrew H. Baker, John P. Cooke

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Despite the importance of nitric oxide signaling in multiple biological processes, its role in tissue regeneration remains largely unexplored. Here, we provide evidence that inducible nitric oxide synthase (iNos) translocates to the nucleus during zebrafish tailfin regeneration and is associated with alterations in the nuclear S-nitrosylated proteome. iNos inhibitors or nitric oxide scavengers reduce protein S-nitrosylation and impair tailfin regeneration. Liquid chromatography/tandem mass spectrometry reveals an increase of up to 11-fold in the number of S-nitrosylated proteins during regeneration. Among these, Kdm1a, a well-known epigenetic modifier, is S-nitrosylated on Cys334. This alters Kdm1a binding to the CoRest complex, thus impairing its H3K4 demethylase activity, which is a response specific to the endothelial compartment. Rescue experiments show S-nitrosylation is essential for tailfin regeneration, and we identify downstream endothelial targets of Kdm1a S-nitrosylation. In this work, we define S-nitrosylation as an essential post-translational modification in tissue regeneration.

Original languageEnglish (US)
Article number6282
JournalNature Communications
Issue number1
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Nuclear S-nitrosylation impacts tissue regeneration in zebrafish'. Together they form a unique fingerprint.

Cite this