Epigenetic regulation by p300: contributonof p300 to overall histone acetylation in vivo, and influence of p300-mediated histone acetylation on other histone modifications

p300 的表观遗传调控：p300 对体内整体组蛋白乙酰化的贡献，以及 p300 介导的组蛋白乙酰化对其他组蛋白修饰的影响

• 批准号: 38191202
• 负责人: Privatdozent Dr. Werner Lutz
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/38191202?language=en
• 关键词: Epigenetic; regulation; p300; contributonof; overall

Normal levels of histone acetylation are maintained by the opposing action of two classes of enzymes, histone deacetylases and histone acetyltransferases. An imbalance of these two enzymatic activities can cause disease. Consequently, pharmacological inhibitors of histone deacetylases have emerged as promising drugs for the epigenetic therapy of various diseases. Yet, the relative contribution of individual enzymes to overall histone acetylation in vivo is unknown.The p300 protein is one of more than 15 proteins with histone acetyltransferase (AT) activity known in mammals and acts as a transcriptional co-regulator for a large number of transcription factors. We have previously shown that a reduction of p300 AT-activity specifically in B-cells of mice affects gene expression and function of mature B-cells, eventually triggering a fatal autoimmune disease. We propose to use primary and immortal B-cells specifically lacking p300 AT-activity to address the role of p300 in overall histone acetylation in vivo. In addition, we will analyse how p300-mediated histone acetylation influences other histone modifications.

组蛋白乙酰化的正常水平是通过两类酶的相反作用来维持的，这两类酶是组蛋白去乙酰化酶和组蛋白乙酰转移酶。这两种酶活性的不平衡可能导致疾病。因此，组蛋白去乙酰化酶的药理学抑制剂已成为各种疾病的表观遗传治疗的有前途的药物。p300蛋白是哺乳动物中已知的15种以上具有组蛋白乙酰转移酶（AT）活性的蛋白质之一，并且作为大量转录因子的转录辅助调节因子。我们以前已经表明，减少p300 AT活性，特别是在B细胞的小鼠影响成熟B细胞的基因表达和功能，最终引发致命的自身免疫性疾病。我们建议使用主要的和不朽的B细胞，特别是缺乏p300 AT活性，以解决的作用，p300在整体组蛋白乙酰化在体内。此外，我们将分析p300介导的组蛋白乙酰化如何影响其他组蛋白修饰。