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Transcriptional regulation of pig GYS1 gene by glycogen synthase kinase 3β (GSK3β)

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Abstract

Glycogen synthase kinase 3β (GSK3β) is a ubiquitous serine/threonine kinase and has important roles in glycogen metabolism biosynthesis. Studies have revealed that GSK3β can directly regulate the glycogen synthase activity, yet little is known about the regulation of GSK3β on GYS1 gene transcription. Here, we show that overexpression of GSK3β decreased the mRNA expression level of GYS1. Then we cloned approximately 1.5 kb of pig GYS1 gene promoter region, generated sequential deletion constructs, and evaluated their activity. A gradual increase of the promoter activity was seen with increasing length of the promoter sequence, reaching its highest activity to the sequence corresponding to nt −350 to +224, and then decreased. However, the activities of constructed promoter fragments show different responses to GSK3β co-transfection. By analyzing a series of GYS1 promoter reporter constructs, we have defined two crucial regions (−1488 to −539, −350 to −147) that are responsible for GSK3β-induced transcriptional repression. Furthermore, the ChIP results revealed that only the first and second NF-κB sites of GYS1 promoter could bind to p65, and overexpression of GSK3β induced a significant decrease in p65 binding to the second NF-κB binding site, suggesting that GSK3β may regulate expression of GYS1 gene through binding to the second rather than the first NF-κB site. These data suggest that the NF-κB plays important roles in the transcriptional activity of pig GYS1 gene regulated by GSK3β.

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Acknowledgements

This study was supported by the grants from the National Natural Science Foundation of China (31101699).

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Authors and Affiliations

  1. Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China

    Yilin Wang, Yan Wang, Tao Zhong, Jiazhong Guo, Li Li, Hongping Zhang & Linjie Wang

  2. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China

    Yilin Wang, Yan Wang, Tao Zhong, Jiazhong Guo, Li Li, Hongping Zhang & Linjie Wang

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  1. Yilin Wang
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  2. Yan Wang
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  3. Tao Zhong
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  4. Jiazhong Guo
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  5. Li Li
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  6. Hongping Zhang
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  7. Linjie Wang
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Correspondence to Linjie Wang.

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Wang, Y., Wang, Y., Zhong, T. et al. Transcriptional regulation of pig GYS1 gene by glycogen synthase kinase 3β (GSK3β). Mol Cell Biochem 424, 203–208 (2017). https://doi.org/10.1007/s11010-016-2856-1

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  • DOI: https://doi.org/10.1007/s11010-016-2856-1

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