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Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice
Core Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein, CBFB. The LH surge increases the expression of Runx1 and Runx2 in ovulatory follicles, while Cbfb is constitutively expressed. To inve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303197/ https://www.ncbi.nlm.nih.gov/pubmed/32555437 http://dx.doi.org/10.1038/s41598-020-64257-0 |
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author | Lee-Thacker, Somang Jeon, Hayce Choi, Yohan Taniuchi, Ichiro Takarada, Takeshi Yoneda, Yukio Ko, CheMyong Jo, Misung |
author_facet | Lee-Thacker, Somang Jeon, Hayce Choi, Yohan Taniuchi, Ichiro Takarada, Takeshi Yoneda, Yukio Ko, CheMyong Jo, Misung |
author_sort | Lee-Thacker, Somang |
collection | PubMed |
description | Core Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein, CBFB. The LH surge increases the expression of Runx1 and Runx2 in ovulatory follicles, while Cbfb is constitutively expressed. To investigate the physiological significance of CBFs, we generated a conditional mutant mouse model in which granulosa cell expression of Runx2 and Cbfb was deleted by the Esr2Cre. Female Cbfb(flox/flox);Esr2(cre/+);Runx2(flox/flox) mice were infertile; follicles developed to the preovulatory follicle stage but failed to ovulate. RNA-seq analysis of mutant mouse ovaries collected at 11 h post-hCG unveiled numerous CBFs-downstream genes that are associated with inflammation, matrix remodeling, wnt signaling, and steroid metabolism. Mutant mice also failed to develop corpora lutea, as evident by the lack of luteal marker gene expression, marked reduction of vascularization, and excessive apoptotic staining in unruptured poorly luteinized follicles, consistent with dramatic reduction of progesterone by 24 h after hCG administration. The present study provides in vivo evidence that CBFs act as essential transcriptional regulators of both ovulation and luteinization by regulating the expression of key genes that are involved in inflammation, matrix remodeling, cell differentiation, vascularization, and steroid metabolisms in mice. |
format | Online Article Text |
id | pubmed-7303197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73031972020-06-22 Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice Lee-Thacker, Somang Jeon, Hayce Choi, Yohan Taniuchi, Ichiro Takarada, Takeshi Yoneda, Yukio Ko, CheMyong Jo, Misung Sci Rep Article Core Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein, CBFB. The LH surge increases the expression of Runx1 and Runx2 in ovulatory follicles, while Cbfb is constitutively expressed. To investigate the physiological significance of CBFs, we generated a conditional mutant mouse model in which granulosa cell expression of Runx2 and Cbfb was deleted by the Esr2Cre. Female Cbfb(flox/flox);Esr2(cre/+);Runx2(flox/flox) mice were infertile; follicles developed to the preovulatory follicle stage but failed to ovulate. RNA-seq analysis of mutant mouse ovaries collected at 11 h post-hCG unveiled numerous CBFs-downstream genes that are associated with inflammation, matrix remodeling, wnt signaling, and steroid metabolism. Mutant mice also failed to develop corpora lutea, as evident by the lack of luteal marker gene expression, marked reduction of vascularization, and excessive apoptotic staining in unruptured poorly luteinized follicles, consistent with dramatic reduction of progesterone by 24 h after hCG administration. The present study provides in vivo evidence that CBFs act as essential transcriptional regulators of both ovulation and luteinization by regulating the expression of key genes that are involved in inflammation, matrix remodeling, cell differentiation, vascularization, and steroid metabolisms in mice. Nature Publishing Group UK 2020-06-18 /pmc/articles/PMC7303197/ /pubmed/32555437 http://dx.doi.org/10.1038/s41598-020-64257-0 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lee-Thacker, Somang Jeon, Hayce Choi, Yohan Taniuchi, Ichiro Takarada, Takeshi Yoneda, Yukio Ko, CheMyong Jo, Misung Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title | Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title_full | Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title_fullStr | Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title_full_unstemmed | Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title_short | Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice |
title_sort | core binding factors are essential for ovulation, luteinization, and female fertility in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303197/ https://www.ncbi.nlm.nih.gov/pubmed/32555437 http://dx.doi.org/10.1038/s41598-020-64257-0 |
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