在H3S10ph和H4K16ac之间的基因组交叉生成一个基因组代码,该代码介导转录延长
Alessio Zippo1, Riccardo Serafini, Marina Rocchigiani
1Dipartimento di Biologia Molecolare Università di Siena, Siena, Italy.
Cell
|September 22, 2009
概括
在10 (H3S10ph) 处的基因组H3酸化启动了一连串激活FOSL1基因转录的过程. 这涉及PIM1激酶,14-3-3,MOF和BRD4,导致增强的RNA聚合酶II过程性.
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.
- 基因规则 基因规则
背景情况:
- 质子修饰,如酸化和乙化,在调节基因转录中起着至关重要的作用.
- 在10 (H3S10ph) 基素H3的酸化与转录激活有关,但精确的分子机制仍然不完全理解.
研究的目的:
- 阐明H3S10ph触发FOSL1基因的转录延长的分子机制.
- 为了确定参与这种信号级联的关键蛋白质和基因素修饰.
主要方法:
- 研究了PIM1激酶在FOSL1增强器中的酸化组素H3中的作用.
- 利用共免疫沉和生化分析来确定14-3-3,MOF和BRD4之间的相互作用.
- 分析了组蛋白修饰 (H3S10ph,H4K16ac) 以及它们对使用染色体免疫沉和RNA测序对转录延长的影响.
主要成果:
- 血清刺激激活PIM1激酶以在FOSL1增强剂中酸化预乙基化组素H3.
- 适应蛋白14-3-3结合H3S10ph核细胞,并招募基因组酸转移酶MOF,导致H4K16ac.
- 这种基因组交叉创建一个H3K9acS10ph/H4K16ac代码,招募BRD4和随后的P-TEFb,它释放暂停的RNA聚合酶II以增强延长.
结论:
- H3S10ph作为FOSL1基因转录延长的关键触发剂.
- 一个涉及PIM1,14-3-3,MOF和BRD4的顺序级联介导H3S10ph诱导的转录.
- 这项研究揭示了一种新的核细胞识别代码 (H3K9acS10ph/H4K16ac),对于招募转录延长因子至关重要.
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