Transcriptional regulation of PEBP1 expression by androgen receptor in mouse testes
Transcriptional regulation of PEBP1 expression by androgen receptor in mouse testes
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小鼠睾丸雄激素受体对 PEBP1 表达的转录调控
DOI：
10.1080/19396368.2021.2004471
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发表时间：
2021-12
影响因子：
2.4
通讯作者：
Hui Liang
中科院分区：
文献类型：
--
作者：
Qiong Deng;Zhu Wang;Ye Du;Ying Zhang;Hui Liang
摘要雄激素和雄激素受体（AR）是维持精子发生和男性生育力的必需物质。先前的研究表明，与野生型小鼠相比，磷脂酰乙醇胺结合蛋白1（Pebp 1）基因在小鼠睾丸支持细胞中AR的选择性消融中下调，表明Pebp 1是AR的候选靶点。本研究的ChIP-PCR数据和ChIP-测序结果证实Pebp 1是AR调控的靶基因。实时PCR、Western印迹分析和免疫荧光数据表明，Pebp 1在睾丸发育的所有阶段都有表达，从出生后1周到8周的发育有增加的趋势。PEBP 1主要位于细胞质中，高强度荧光显示PEBP位于睾丸小管的管腔中。生物信息学分析表明，有效的雄激素反应元件（战神）位于Pepb 1基因启动子区。双荧光实验结果表明雄激素和AR可与Pebp 1的战神结合，诱导基因表达增加。提示Pepb 1是一个新发现的受雄激素和AR调控的小鼠睾丸支持细胞靶基因。但其在精子发生中作用的详细分子机制仍需进一步研究。缩略语名称：应收账款：雄激素受体; Pebp 1：磷脂酰乙醇胺结合蛋白1; ARKO：雄激素受体敲除; WT：野生型; SCARKO：支持细胞选择性雄激素受体敲除; ChIP：染色质免疫沉淀; RKIP：Raf激酶抑制蛋白; MAPK：促分裂原活化蛋白激酶; NF-κB：活化B细胞的核因子κ-轻链增强子; GSK-3：糖原合成酶激酶-3; RT-PCR：逆转录酶聚合酶链反应; SEM：平均值的标准误差
ABSTRACT Androgen and AR are essential for maintaining spermatogenesis and male fertility. Previous studies have shown that the phosphatidyl ethanolamine binding protein 1 (Pebp1) gene is down-regulated in the selective ablation of the AR in the Sertoli cells of mouse testes compared with wild-type mice, indicating that Pebp1 is a candidate target of AR. The ChIP-PCR data and ChIP-sequencing results of this study verified that Pebp1 is a target gene regulated by AR. Real-time PCR, Western blot analysis, and immunofluorescence data showed that Pebp1 is expressed at all stages of testicular development, with an increasing trend from 1 to 8 weeks of postnatal development. PEBP1 was principally located in the cytoplasm, and high-intensity fluorescence revealed PEBP in the lumen of the testicular tubules. Bioinformatics analysis indicated effective androgen-responsive elements (AREs) located in the promotor of Pepb1 gene. Dual fluorescence assay data showed that androgens and AR could bind to the AREs of Pebp1 and induce an increase of gene expression. These data suggest that Pepb1 is a newfound target gene regulated by androgens and AR in mouse Sertoli cells. However, the detailed molecular mechanism of their role in spermatogenesis still needs to be further studied. Abbreviations: AR: androgen receptor; Pebp1: phosphatidyl ethanolamine binding protein 1; ARKO: androgen receptor knockout; WT: wild type; SCARKO: Sertoli cell-selective androgen receptor knockout; ChIP: chromatin immunoprecipitation; RKIP: Raf kinase inhibitory protein; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; GSK-3: glycogen synthase kinase-3; RT-PCR: reverse transcriptase polymerase chain reaction; SEM: standard error of the mean
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影响因子：
5.2
作者：
Ahmed M;Lai TH;Zada S;Hwang JS;Pham TM;Yun M;Kim DR
通讯作者：
Kim DR
影响因子：
2.8
作者：
Kasimanickam, R. K.;Kasimanickam, V. R.;Kastelic, J. P.
通讯作者：
Kastelic, J. P.
影响因子：
2.9
作者：
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通讯作者：
Qiaoxia Zhang;Xiao-Yan Zhang;Zhen-Ming Zhang;Wei Lu;Ling Liu;Gang Li;Z. Cai;Y. Gui;Chawnshang Chang
影响因子：
3.6
作者：
Chen, Min;Wang, Xiaona;Gao, Fei
通讯作者：
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影响因子：
3.8
作者：
Gibbons, R;Adeoya-Osiguwa, SA;Fraser, LR
通讯作者：
Fraser, LR