GATA5 SUMOylation is indispensable for zebrafish cardiac development
Bin Wen
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Hao Yuan
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Xiaohui Liu
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Haihong Wang
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Saijuan Chen
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Zhu Chen
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Hugues de The
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
,
Jun Zhou
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
,
Jun Zhu
(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
1
USTC -
University of Science and Technology of China [Hefei]
2 LGF-ENSMSE - Laboratoire Georges Friedel
3 IAC RWTH - Institute of Inorganic Chemistry [Aachen]
4 GRDF - Gaz Réseau Distribution France
5 Shanghai Jiao Tong University School of Medicine
6 SCUT - South China University of Technology [Guangzhou]
7 CNRS-LIA124 - French-Chinese Research Center for Life Sciences and Genomics
8 INSERM U944 Laboratoire de Pathologie et Virologie Moléculaire
9 Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire
10 UPD7 - Université Paris Diderot - Paris 7
11 Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris]
12 Collège de France - Chaire Oncologie cellulaire et moléculaire
13 State Key Laboratory of Analytical Chemistry for Life Science [School of Chemistry and Chemical Engineering, Nanjing University]
14 Tongji University
15 CIRB - Centre interdisciplinaire de recherche en biologie
2 LGF-ENSMSE - Laboratoire Georges Friedel
3 IAC RWTH - Institute of Inorganic Chemistry [Aachen]
4 GRDF - Gaz Réseau Distribution France
5 Shanghai Jiao Tong University School of Medicine
6 SCUT - South China University of Technology [Guangzhou]
7 CNRS-LIA124 - French-Chinese Research Center for Life Sciences and Genomics
8 INSERM U944 Laboratoire de Pathologie et Virologie Moléculaire
9 Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire
10 UPD7 - Université Paris Diderot - Paris 7
11 Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris]
12 Collège de France - Chaire Oncologie cellulaire et moléculaire
13 State Key Laboratory of Analytical Chemistry for Life Science [School of Chemistry and Chemical Engineering, Nanjing University]
14 Tongji University
15 CIRB - Centre interdisciplinaire de recherche en biologie
Bin Wen
- Fonction : Auteur
Hao Yuan
- Fonction : Auteur
Xiaohui Liu
- Fonction : Auteur
Haihong Wang
- Fonction : Auteur
Saijuan Chen
- Fonction : Auteur
Zhu Chen
- Fonction : Auteur
Hugues de The
- Fonction : Auteur
- PersonId : 754068
- IdHAL : hugues-the-de
- ORCID : 0000-0002-1113-4472
Jun Zhou
- Fonction : Auteur
Jun Zhu
- Fonction : Auteur
Résumé
Background: SUMOylation is a critical regulatory protein modification in eukaryotic cells and plays a pivotal role in cardiac development and disease. Several cardiac transcription factors are modified by SUMO, but little is known about the impact of SUMOylation on their function during cardiac development. Methods: We used a zebrafish model to address the impact of SUMOylation on GATA5, an essential transcription factor in zebrafish cardiac development. GATA5 SUMOylation was probed by western blot, the subcellular localization and transcriptional activity of GATA5 mutants were examined by immunostaining and luciferase reporter assay. The in vivo function of GATA5 SUMOylation was evaluated by gata5 mutants mRNA microinjection and in situ hybridization in gata5 morphants and ubc9 mutants. Results: Firstly, we identified GATA5 as a SUMO substrate, and lysine 324 (K324) and lysine 360 (K360) as two major modification sites. Conversion of lysine to arginine at these two sites did not affect subcellular localization, but did affect the transcriptional activity of GATA5. Secondly, in vivo experiments demonstrated that the wild type (WT) and K324R mutant of gata5 could rescue impaired cardiac precursor differentiation, while the K360R mutant of gata5 drastically lost this potency in gata5 morphant. Furthermore, in SUMOylationdeficient ubc9 mutants, the abnormal expression pattern displayed by the early markers of cardiac development (nkx2.5 and mef2cb) could be restored using a sumo-gata5 fusion, but not with a WT gata5. Conclusion: GATA5 SUMOylation is indispensable for early zebrafish cardiac development. General significance: Our studies highlight the potential importance of transcription factor SUMOylation in cardiac development.