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Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes
BACKGROUND: Enhancer of zeste homologue 2 (EZH2), the core member of polycomb repressive complex 2 (PRC2), has multiple splicing modes and performs various physiological functions. However, function and mechanism of alternative splicing at Ezh2 exon 3 in reproduction are unknown. METHODS: We generat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254527/ https://www.ncbi.nlm.nih.gov/pubmed/35791029 http://dx.doi.org/10.1186/s12958-022-00962-x |
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author | Guo, Shi-meng Liu, Xing-ping Tian, Qing Fei, Cai-feng Zhang, Yi-ran Li, Zhi-ming Yin, Ying He, Ximiao Zhou, Li-quan |
author_facet | Guo, Shi-meng Liu, Xing-ping Tian, Qing Fei, Cai-feng Zhang, Yi-ran Li, Zhi-ming Yin, Ying He, Ximiao Zhou, Li-quan |
author_sort | Guo, Shi-meng |
collection | PubMed |
description | BACKGROUND: Enhancer of zeste homologue 2 (EZH2), the core member of polycomb repressive complex 2 (PRC2), has multiple splicing modes and performs various physiological functions. However, function and mechanism of alternative splicing at Ezh2 exon 3 in reproduction are unknown. METHODS: We generated Ezh2(Long) and Ezh2(Short) mouse models with different point mutations at the Ezh2 exon 3 alternative splicing site, and each mutant mouse model expressed either the long or the short isoform of Ezh2. We examined mutant mouse fertility and oocyte development to assess the function of Ezh2 alternative splicing at exon 3 in the reproductive system. RESULTS: We found that Ezh2(Long) female mice had normal fertility. However, Ezh2(Short) female mice had significantly decreased fertility and obstructed oogenesis, with compromised mitochondrial function in Ezh2(Short) oocytes. Interestingly, increased EZH2 protein abundance and accumulated H3K27me3 were observed in Ezh2(Short) oocytes. CONCLUSIONS: Our results demonstrate that correct Ezh2 alternative splicing at exon 3 is important for mouse oogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-022-00962-x. |
format | Online Article Text |
id | pubmed-9254527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92545272022-07-06 Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes Guo, Shi-meng Liu, Xing-ping Tian, Qing Fei, Cai-feng Zhang, Yi-ran Li, Zhi-ming Yin, Ying He, Ximiao Zhou, Li-quan Reprod Biol Endocrinol Research BACKGROUND: Enhancer of zeste homologue 2 (EZH2), the core member of polycomb repressive complex 2 (PRC2), has multiple splicing modes and performs various physiological functions. However, function and mechanism of alternative splicing at Ezh2 exon 3 in reproduction are unknown. METHODS: We generated Ezh2(Long) and Ezh2(Short) mouse models with different point mutations at the Ezh2 exon 3 alternative splicing site, and each mutant mouse model expressed either the long or the short isoform of Ezh2. We examined mutant mouse fertility and oocyte development to assess the function of Ezh2 alternative splicing at exon 3 in the reproductive system. RESULTS: We found that Ezh2(Long) female mice had normal fertility. However, Ezh2(Short) female mice had significantly decreased fertility and obstructed oogenesis, with compromised mitochondrial function in Ezh2(Short) oocytes. Interestingly, increased EZH2 protein abundance and accumulated H3K27me3 were observed in Ezh2(Short) oocytes. CONCLUSIONS: Our results demonstrate that correct Ezh2 alternative splicing at exon 3 is important for mouse oogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-022-00962-x. BioMed Central 2022-07-05 /pmc/articles/PMC9254527/ /pubmed/35791029 http://dx.doi.org/10.1186/s12958-022-00962-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Guo, Shi-meng Liu, Xing-ping Tian, Qing Fei, Cai-feng Zhang, Yi-ran Li, Zhi-ming Yin, Ying He, Ximiao Zhou, Li-quan Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title | Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title_full | Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title_fullStr | Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title_full_unstemmed | Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title_short | Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes |
title_sort | regulatory roles of alternative splicing at ezh2 gene in mouse oocytes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254527/ https://www.ncbi.nlm.nih.gov/pubmed/35791029 http://dx.doi.org/10.1186/s12958-022-00962-x |
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