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On-line Access: 2021-12-14
Received: 2021-04-27
Revision Accepted: 2021-07-14
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Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN. ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2100393 @article{title="ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells", %0 Journal Article TY - JOUR
ERα通过在乳腺癌细胞中建立富含H3K27ac修饰的染色质微环境促进抑癌基因ApoA-I的转录创新点:本研究在细胞层面上证明了ApoA-I具有抑癌功能,另外结合体外实验以及TCGA数据分析,首次发现乳腺癌细胞中ApoA-I是ERα的直接靶基因,这为理解ERα在乳腺癌中的双刃剑作用提供了新的切入点。同时,我们猜测雌激素替代疗法联合ApoA-I模拟肽给药可能会增强luminal(ERα表达阳性)型乳腺癌的治疗效果。 方法:通过干预E2/ERα信号通路(用雌激素受体拮抗剂ICI182780降解ERα;激素剥夺后加入E2激活E2/ERα信号通路;在三阴性乳腺癌细胞MDA-MB-231中过表达ERα),观察ApoA-I转录水平的变化;通过用ERα抗体进行ChIP-seq结合序列分析探究ERα是否直接调控ApoA-I转录;在激素剥夺或ICI182780处理的条件下用组蛋白H3赖氨酸27位点乙酰化(H3K27ac)抗体进行ChIP-seq或ChIP-qPCR,结合乙酰转移酶p300抑制剂处理,探究ERα调控ApoA-I转录的具体机制。 结论:ERα能够直接结合在ApoA-I基因的最后一个外显子上促进ApoA-I的转录,且该结合位点上有一个雌激素响应元件(ERE);p300可能作为ERα的一个共激活因子,通过建立富含H3K27ac的染色质微环境来激活ApoA-I的转录。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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