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INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion

The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self‐renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of...

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Autores principales: Xian, Shu, Zhang, Yan, Wang, Li, Yao, Fang, Ding, Jinli, Wang, Yanqing, Yang, Xiao, Dai, Fangfang, Yin, Tailang, Cheng, Yanxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051727/
https://www.ncbi.nlm.nih.gov/pubmed/33724648
http://dx.doi.org/10.1111/jcmm.16322
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author Xian, Shu
Zhang, Yan
Wang, Li
Yao, Fang
Ding, Jinli
Wang, Yanqing
Yang, Xiao
Dai, Fangfang
Yin, Tailang
Cheng, Yanxiang
author_facet Xian, Shu
Zhang, Yan
Wang, Li
Yao, Fang
Ding, Jinli
Wang, Yanqing
Yang, Xiao
Dai, Fangfang
Yin, Tailang
Cheng, Yanxiang
author_sort Xian, Shu
collection PubMed
description The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self‐renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high‐throughput sequencing (RNA‐seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA‐seq combined with high‐throughput sequencing (ChIP‐seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion‐associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion‐associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies.
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spelling pubmed-80517272021-04-21 INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion Xian, Shu Zhang, Yan Wang, Li Yao, Fang Ding, Jinli Wang, Yanqing Yang, Xiao Dai, Fangfang Yin, Tailang Cheng, Yanxiang J Cell Mol Med Original Articles The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self‐renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high‐throughput sequencing (RNA‐seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA‐seq combined with high‐throughput sequencing (ChIP‐seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion‐associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion‐associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies. John Wiley and Sons Inc. 2021-03-16 2021-04 /pmc/articles/PMC8051727/ /pubmed/33724648 http://dx.doi.org/10.1111/jcmm.16322 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xian, Shu
Zhang, Yan
Wang, Li
Yao, Fang
Ding, Jinli
Wang, Yanqing
Yang, Xiao
Dai, Fangfang
Yin, Tailang
Cheng, Yanxiang
INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title_full INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title_fullStr INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title_full_unstemmed INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title_short INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
title_sort ino80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051727/
https://www.ncbi.nlm.nih.gov/pubmed/33724648
http://dx.doi.org/10.1111/jcmm.16322
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