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PLZF 通过结合分化相关基因抑制小鼠精原干细胞的分化。

PLZF suppresses differentiation of mouse spermatogonial progenitor cells via binding of differentiation associated genes.

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

出版信息

J Cell Physiol. 2020 Mar;235(3):3033-3042. doi: 10.1002/jcp.29208. Epub 2019 Sep 20.

Abstract

Promyelocytic leukaemia zinc finger (PLZF) is a key factor in inhibiting differentiation of spermatogonial progenitor cells (SPCs), but the underlying mechanisms are still largely unknown. In this study, the regulation of PLZF on Kit, Stra8, Sohlh2, and Dmrt1 (SPCs differentiation related genes) was investigated. We found some PLZF potential binding sites existed in the promoters of Kit, Stra8, Sohlh2, and Dmrt1. Additionally, the expressions of KIT, STRA8, SOHLH2, and DMRT1 were upregulated when PLZF was knockdown in SPCs. Furthermore, chromatin immunoprecipitation quantitative polymerase chain reaction revealed PLZF directly bound to the promoters of Kit, Stra8, Sohlh2, and Dmrt1. Besides, dual luciferase assay verified PLZF repressed those gene expressions. Collectively, our finding indicate that PLZF binds to the promoter regions of Kit, Stra8, Sohlh2, and Dmrt1 to regulate SPCs differentiation, which facilitate us to further understand the regulatory mechanism of PLZF in SPCs fates.

摘要

早幼粒细胞白血病锌指蛋白(PLZF)是抑制精原干细胞(SPCs)分化的关键因素,但其中的作用机制在很大程度上仍不清楚。在本研究中,我们研究了 PLZF 对 Kit、Stra8、Sohlh2 和 Dmrt1(SPCs 分化相关基因)的调控作用。我们发现 Kit、Stra8、Sohlh2 和 Dmrt1 的启动子上存在一些 PLZF 的潜在结合位点。此外,当 SPCs 中的 PLZF 被敲低时,KIT、STRA8、SOHLH2 和 DMRT1 的表达上调。此外,染色质免疫沉淀定量聚合酶链反应显示 PLZF 直接结合到 Kit、Stra8、Sohlh2 和 Dmrt1 的启动子上。此外,双荧光素酶报告基因检测验证了 PLZF 对这些基因表达的抑制作用。综上所述,我们的研究结果表明,PLZF 结合到 Kit、Stra8、Sohlh2 和 Dmrt1 的启动子区域,以调节 SPCs 的分化,这有助于我们进一步了解 PLZF 在 SPCs 命运中的调控机制。

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