Rev-Erbs通过抑制增强剂导向的转录来抑制巨细胞基因表达
Michael T Y Lam1, Han Cho, Hanna P Lesch
1Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|June 4, 2013
概括
Rev-Erb核受体通过抑制增强剂衍生RNA (eRNA) 转录来调节基因表达. 这种机制建立了细胞特异性基因抑制,突出了eRNAs.
科学领域:
- 分子生物学分子生物学
- 基因法规 基因法规
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- Rev-Erb核受体 (Rev-Erb-α和Rev-Erb-β) 是已知的昼夜节律,新陈代谢和炎症的调节者.
- Rev-Erbs通过招募共抑制器复合体来准基因调节元件,作为转录抑制剂发挥作用.
- 由Rev-Erbs进行细胞特异性抑制的分子机制尚不清楚.
研究的目的:
- 研究Rev-Erbs在巨细胞特异性基因表达程序中的作用.
- 阐明Rev-Erbs调解转录抑制的机制.
- 确定增强剂衍生RNAs (eRNAs) 在基因调节中的功能意义.
主要方法:
- 利用小鼠巨细胞作为一个模型系统.
- 采用了经过修改的全球运行测序技术,精确地绘制了eRNAs新生的5'端.
- 进行了eRNA的向降解,以评估它们对基因表达的功能影响.
主要成果:
- Rev-Erbs抑制了由巨细胞谱系因子选择的远端增强剂的功能,从而建立了巨细胞特异性抑制.
- Rev-Erb介导的抑制与抑制增强剂衍生RNA (eRNA) 转录有关.
- 针对性降解eRNAs减少了附近信使RNAs的表达,表明eRNAs在增强器功能中的直接作用.
- 增强剂活动转移到促进体需要转录因子结合点和特定的eRNA编码序列.
结论:
- Rev-Erbs通过抑制远端增强剂的eRNA转录来抑制基因表达.
- eRNA在增强器功能和基因调节中发挥着直接作用.
- 这些发现揭示了由Rev-Erbs和eRNAs介导的细胞特异性基因抑制的新机制.
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