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Zhaoxia Huang, Ling Wang, Xiaohui Hu, Zhengfeng Wang, Zachary G Woodward, Shuai Li, Quan Dong Nguyen, David W Li, Lens; Sumoylation Regulation of Lens Differentiation.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2639.
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© ARVO (1962-2015); The Authors (2016-present)
The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. In ocular tissues, sumoylation helps to determine the differentiation of cone verse rod photoreceptors. Our recent study revealed that SUMO1-mediated sumoylation is an indispensable step towards activation of p32 Pax-6, a master regulator of eye and brain development (Yan et al. 2010. PNAS). While the effects of sumoylation on individual targets in regulating cell differentiation and other biological processes are being unraveled, it remains largely unknown how SUMO isoforms regulate cell differentiation and whether SUMO1 and SUMO2/3 display distinct functions. Here, we determined the functional differences between SUMO isoforms and analyzed their mechanisms of action.
Electrophoretic mobility shifting assays (EMSA) was used to detect the interactions between TFs and the cis-elements. Reporter gene activity assays and in vitro mutagenesis were used to determine the specific activities of TFs promoter. ChIP assays were used to determine the in vivo binding of TFs. QRT-PCR, Immunocytochemistry and Western blot analysis were used for detection of gene expression.
SUMO1 and SUMO2/3 display significant differences in abundance, localization and substrate targets. SUMO1 can promote lens differentiation, but SUMO2 and 3 inhibit it. Mechanistically, the specificity protein 1 (SP1) plays an important role in mediating the differential functions of the different SUMO isoforms. SUMO1 -conjugation of SP1 stimulates its activity on the downstream target genes such as b-crystallin genes. In contrast, SUMO2/3-mediated modification of SP1 attenuates its transcription activity via numerous mechanisms.
SUMO isoforms differentially regulate different transcription factors or the same transcription factor to exert differential control on lens differentiation. (Supported by Research Prevent Blindness, Zhongshan Ophthalmic Center and Chinese Scholarship Council)
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