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Identification of estrogen receptor target genes involved in gonadal feminization caused by estrogen in Xenopus laevis
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2021-01-21 , DOI: 10.1016/j.aquatox.2021.105760
Yuanyuan Li , Jinbo Li , Yanping Shen , Yiming Xiong , Xinghong Li , Zhanfen Qin

Estrogens and estrogenic endocrine disrupting chemicals can cause gonadal feminization in some vertebrates mainly through estrogen receptor (ER), but the underlying molecular mechanisms are unclear. The present study aimed to identify ER target genes involved in estrogen-caused gonadal feminization in Xenopus laevis. Based on our recent transcriptomic data that 10 nM 17β-estradiol (E2) altered gene transcription in feminizing gonads of male X. laevis at NF stages 48, 50, and 52, we searched estrogen response element (ERE) using the Dragon ERE Finder software in the promoter region of all the E2-regulated genes. As a result, 163 genes containing ERE sequence were identified as predicted ER target genes at NF stage 50 (on the 14th day postfertilization), a crucial stage for gonadal feminization. Then, some of these predicted ER target genes were further investigated, mainly including the genes that were suggested to be involved in E2-caused gonadal feminization and genes being dramatically up or down-regulated by E2. Fifteen genes were demonstrated to be responsive to E2, in turn ER antagonist blocked the E2-regulated transcription. Finally, we identified 10 genes that can bind to ERα by a chromatin immunoprecipitation-qPCR. Taken together, we identified the 10 genes that contain predicted ERE sequences, are responsive to estrogen and ER antagonist, and have ability to bind to ER as ER target genes, including pglyrp2, apoa1, fgb, tdo2, ca6, nags, cpb2, tmprss6, nudc, zwilch. Our results could help to improve the understanding of the molecular mechanisms for gonadal feminization caused by estrogenic endocrine disrupting chemicals in X. laevis, and even in other species.



中文翻译:

爪蟾雌激素引起的性腺女性化的雌激素受体靶基因的鉴定

雌激素和破坏雌激素的内分泌化学物质可能主要通过雌激素受体(ER)导致某些脊椎动物的性腺女性化,但潜在的分子机制尚不清楚。本研究旨在鉴定非洲爪蟾中雌激素引起的性腺女性化的ER靶基因根据我们最近的转录组数据是10纳米17 β雌二醇(E2)在女性化的男性性腺改变基因转录非洲爪蟾在NF阶段48、50和52,我们使用Dragon ERE Finder软件在所有E2调控基因的启动子区域中搜索雌激素反应元件(ERE)。结果,含有163个含有ERE序列的基因在NF阶段50(受精后第14天)被确定为预测的ER靶基因,这是性腺女性化的关键阶段。然后,进一步研究了其中一些预测的ER靶基因,主要包括被认为与E2导致的性腺女性化有关的基因以及被E2显着上调或下调的基因。已证明有15个基因对E2有反应,而ER拮抗剂又阻断了E2调控的转录。最后,我们通过染色质免疫沉淀-qPCR鉴定了可以与ERα结合的10个基因。在一起pglyrp2载脂蛋白A1FGBTDO2CA6耿耿于怀CPB2TMPRSS6NUDCzwilch。我们的结果可能有助于增进对由X. laevis甚至其他物种中的雌激素内分泌干扰化学物质引起的性腺女性化分子机制的理解。

更新日期:2021-01-28
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