TRIM24将一个非正规的组织蛋白签名与乳腺癌联系起来
Wen-Wei Tsai1, Zhanxin Wang, Teresa T Yiu
1Department of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Nature
|December 18, 2010
概括
染色体调节器TRIM24通过其PHD-Bromo区域识别双核素标记 (H3K4me0和H3K23ac). 这一功能对于激活参与细胞增殖和癌症发展的基因至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 结构生物学 结构生物学
背景情况:
- 基因组蛋白修饰是基因表达的关键调节者.
- 染色体读取蛋白解释这些修饰.
- 同时识别多个组素标记允许复杂的信号.
研究的目的:
- 为了研究含有24 (TRIM24) 三方图案的作用,作为双核素标记的读者.
- 阐明TRIM24识别特定基因素修饰的结构基础.
- 了解TRIM24在基因激活中的功能及其对癌症的影响.
主要方法:
- 进行X射线晶体学以确定TRIM24 PHD-Bromo区域的3D结构.
- 染色体免疫沉测定用于评估TRIM24结合.
- 对基因表达数据和患者存活率的分析.
主要成果:
- TRIM24的功能是读取双质子标记:未修改的H3K4 (H3K4me0) 和乙化H3K23 (H3K23ac).
- TRIM24 的 PHD-Bromo 区域构成一个单一的组合基因素标记识别单元.
- TRIM24与染色质和雌激素受体结合,激活与增殖和瘤发展相关的雌激素依赖基因.
结论:
- TRIM24使用非正规的组织蛋白签名来激活染色体.
- 异常的TRIM24表达与乳腺癌患者的生存率降低有关.
- TRIM24代表了理解和潜在治疗癌症发病的新目标.
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