STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

Ou-Yang, Huan; Wu, Shinn-Chih; Sung, Li-Ying; Yang, Shiao-Hsuan; Yang, Shang-Hsun; Chong, Kowit-Yu; Chen, Chuan-Mu

doi:10.3390/ijms22010460

Open AccessArticle

STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

by

Huan Ou-Yang

^1,2,3,†,

Shinn-Chih Wu

^2,†,

Li-Ying Sung

^3,†

,

Shiao-Hsuan Yang

^1,4,

Shang-Hsun Yang

^5,6,

Kowit-Yu Chong

^7,8

and

Chuan-Mu Chen

^1,9,*

¹

Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan

²

Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan

³

Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan

⁴

Reproductive Medicine Center, Department of Gynecology, Changhua Christian Hospital, Changhua 515, Taiwan

⁵

Department of Physiology, National Cheng Kung University, Tainan 70101, Taiwan

⁶

Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan

⁷

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁸

Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan

⁹

The iEGG and Animal Biotechnology Center, and Rong-Hsing Translational Medicine Research Center, National Chung Hsing University, Taichung 402, Taiwan

^*

Author to whom correspondence should be addressed.

^†

Authors contributed equally to this work.

Int. J. Mol. Sci. 2021, 22(1), 460; https://doi.org/10.3390/ijms22010460

Submission received: 29 November 2020 / Revised: 19 December 2020 / Accepted: 31 December 2020 / Published: 5 January 2021

(This article belongs to the Special Issue Regulation of Gene Expression During Embryonic Development)

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Abstract

The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse zygotes to the two-cell stage. Our previous study reported that mouse granzyme g (Gzmg), a serine-type protease, is required for the MZT. In this study, we further identified the maternal factors that regulate the Gzmg promoter activity in the zygote to the two-cell stage of mouse embryos. A full-length Gzmg promoter from mouse genomic DNA, FL-pGzmg (−1696~+28 nt), was cloned, and four deletion constructs of this Gzmg promoter, Δ1-pGzmg (−1369~+28 nt), Δ2-pGzmg (−939~+28 nt), Δ3-pGzmg (−711~+28 nt) and Δ4-pGzmg (−417~+28 nt), were subsequently generated. Different-sized Gzmg promoters were used to perform promoter assays of mouse zygotes and two-cell stage embryos. The results showed that Δ4-pGzmg promoted the highest expression level of the enhanced green fluorescent protein (EGFP) reporter in the zygotes and two-cell embryos. The data suggested that time-specific transcription factors upregulated Gzmg by binding cis-elements in the −417~+28-nt Gzmg promoter region. According to the results of the promoter assay, the transcription factor binding sites were predicted and analyzed with the JASPAR database, and two transcription factors, signal transducer and activator of transcription 3 (STAT3) and GA-binding protein alpha (GABPα), were identified. Furthermore, STAT3 and GABPα are expressed and located in zygote pronuclei and two-cell nuclei were confirmed by immunofluorescence staining; however, only STAT3 was recruited to the mouse zygote pronuclei and two-cell nuclei injected with the Δ4-pGzmg reporter construct. These data indicated that STAT3 is a maternal transcription factor and may upregulate Gzmg to promote the MZT. Furthermore, treatment with a STAT3 inhibitor, S3I-201, caused mouse embryonic arrest at the zygote and two-cell stages. These results suggest that STAT3, a maternal protein, is a critical transcription factor and regulates Gzmg transcription activity in preimplantation mouse embryos. It plays an important role in the maternal-to-zygotic transition during early embryonic development.

Keywords: STAT3; granzyme g; preimplantation embryo; maternal-to-zygotic transition

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MDPI and ACS Style

Ou-Yang, H.; Wu, S.-C.; Sung, L.-Y.; Yang, S.-H.; Yang, S.-H.; Chong, K.-Y.; Chen, C.-M. STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos. Int. J. Mol. Sci. 2021, 22, 460. https://doi.org/10.3390/ijms22010460

AMA Style

Ou-Yang H, Wu S-C, Sung L-Y, Yang S-H, Yang S-H, Chong K-Y, Chen C-M. STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos. International Journal of Molecular Sciences. 2021; 22(1):460. https://doi.org/10.3390/ijms22010460

Chicago/Turabian Style

Ou-Yang, Huan, Shinn-Chih Wu, Li-Ying Sung, Shiao-Hsuan Yang, Shang-Hsun Yang, Kowit-Yu Chong, and Chuan-Mu Chen. 2021. "STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos" International Journal of Molecular Sciences 22, no. 1: 460. https://doi.org/10.3390/ijms22010460

APA Style

Ou-Yang, H., Wu, S.-C., Sung, L.-Y., Yang, S.-H., Yang, S.-H., Chong, K.-Y., & Chen, C.-M. (2021). STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos. International Journal of Molecular Sciences, 22(1), 460. https://doi.org/10.3390/ijms22010460

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STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

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