Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2019; 15(1):69-80. doi:10.7150/ijbs.28129 This issue Cite

Research Paper

Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System

Danyang Li*, Hui-Li Wang*, Xiyao Huang, Xiaozhen Gu, Weizhen Xue, Yi Xu✉

School of Food Science and Engineering, Hefei University of Technology, No. 193 of Tunxi Road, Baohe District, Hefei, Anhui Province, China
*These authors contributed equally to the work.

✉ Corresponding author: xuyiedu.cn

Citation:
Li D, Wang HL, Huang X, Gu X, Xue W, Xu Y. Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System. Int J Biol Sci 2019; 15(1):69-80. doi:10.7150/ijbs.28129. https://www.ijbs.com/v15p0069.htm
Other styles

File import instruction

Abstract

Graphic abstract

EZH2 plays vital roles in epigenetic regulation, neuronal development and cancer progression. Here a novel EZH2 variant, namely EZH2-X9 (X9 for short) resulting from alternative splicing, was isolated, identified and functionally characterized. X9 was highly expressed in the brains of SD rats, indicating a potentially distinguished role in the central nervous system (CNS). Owing to a transcript profiling, X9 was enriched in multiple brain regions at very early stage of life. Immunostaining validated the presence of the protein form of X9, which was localized similarly with the wild-type form, EZH2-WT. To investigate the functional consequence of X9, genetic intervention was performed in PC-12 cell line, a classic cellular model for neuronal development. It revealed that the depletion of either variant was sufficient to impair neuronal proliferation and differentiation significantly, an evidence that roles of X9 could not be complemented by EZH2-WT. Considering epigenetic regulation, X9 lost the capability to recruit the histone mark H3K27me3, but retained the cooperation with EED, as well as the repressive aspects in governing gene expression. Nonetheless, through profiling the genes affected, it's discovered that EZH2-WT and X9 markedly differed in their regulatory targets, as X9 intended to repress cell cycle- and autophagy-related genes, like GSK and MapILC3. Overall, a novel Ezh2 variant was characterized in the mammal CNS, providing insight with the structural and functional delineation of this key developmental switch, Ezh2.

Keywords: Ezh2, splicing variant, neuronal differentiation, H3K27me3

Citation styles

APA
Li, D., Wang, H.L., Huang, X., Gu, X., Xue, W., Xu, Y. (2019). Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System. International Journal of Biological Sciences, 15(1), 69-80. https://doi.org/10.7150/ijbs.28129.

ACS
Li, D.; Wang, H.L.; Huang, X.; Gu, X.; Xue, W.; Xu, Y. Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System. Int. J. Biol. Sci. 2019, 15 (1), 69-80. DOI: 10.7150/ijbs.28129.

NLM
Li D, Wang HL, Huang X, Gu X, Xue W, Xu Y. Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System. Int J Biol Sci 2019; 15(1):69-80. doi:10.7150/ijbs.28129. https://www.ijbs.com/v15p0069.htm

CSE
Li D, Wang HL, Huang X, Gu X, Xue W, Xu Y. 2019. Identification and Functional Characterization of a New Splicing Variant of EZH2 in the Central Nervous System. Int J Biol Sci. 15(1):69-80.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use