Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice

Abstract 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...

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Autores principales:	Somang Lee-Thacker, Hayce Jeon, Yohan Choi, Ichiro Taniuchi, Takeshi Takarada, Yukio Yoneda, CheMyong Ko, Misung Jo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d5f1b8574d942ac9a1a967e2817153e
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spelling	oai:doaj.org-article:3d5f1b8574d942ac9a1a967e2817153e2021-12-02T17:41:08ZCore Binding Factors are essential for ovulation, luteinization, and female fertility in mice10.1038/s41598-020-64257-02045-2322https://doaj.org/article/3d5f1b8574d942ac9a1a967e2817153e2020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-64257-0https://doaj.org/toc/2045-2322Abstract 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.Somang Lee-ThackerHayce JeonYohan ChoiIchiro TaniuchiTakeshi TakaradaYukio YonedaCheMyong KoMisung JoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Somang Lee-Thacker Hayce Jeon Yohan Choi Ichiro Taniuchi Takeshi Takarada Yukio Yoneda CheMyong Ko Misung Jo Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice
description	Abstract 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	article
author	Somang Lee-Thacker Hayce Jeon Yohan Choi Ichiro Taniuchi Takeshi Takarada Yukio Yoneda CheMyong Ko Misung Jo
author_facet	Somang Lee-Thacker Hayce Jeon Yohan Choi Ichiro Taniuchi Takeshi Takarada Yukio Yoneda CheMyong Ko Misung Jo
author_sort	Somang Lee-Thacker
title	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_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_sort	core binding factors are essential for ovulation, luteinization, and female fertility in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3d5f1b8574d942ac9a1a967e2817153e
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Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice

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