Characterization of candidate histone methyltransferases

候选组蛋白甲基转移酶的表征

• 批准号: 7292925
• 负责人: David Eric Symer
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7292925
• 关键词: Characterization; candidate; histone; methyltransferases

We conducted a comprehensive analysis of transcription of two candidate histone methyltransferases in human and mouse tissues, revealing tissue-specific expression of alternatively spliced and read-through transcripts. A major fraction of read-through transcripts may add an encoded protein domain modifying specificity of one the candidates. A manuscript is in preparation on this work. We conducted several yeast two-hybrid screens to identify protein-binding partners for the putative histone methyltransferases. These screens yielded several intriguing candidates that are being characterized further by biochemical and genetic methods in mammalian cells and in vitro. We have generated a conditional knockout mouse model lacking one of the putative histone methyltransferases located on a frequently deleted chromosomal region. The knockout mice could comprise a new model for chronic lymphocytic leukemia, for asthma, and/or for other cancers or human diseases.

我们对人类和小鼠组织中两种候选组蛋白甲基转移酶的转录进行了全面分析，揭示了选择性剪接和可读转录本的组织特异性表达。大部分的可读转录本可能增加一个编码的蛋白质结构域修饰特异性的候选物。关于这项工作的手稿正在准备中。我们进行了几次酵母双杂交筛选，以确定假定的组蛋白甲基转移酶的蛋白质结合伙伴。这些筛选产生了几个有趣的候选者，正在通过生物化学和遗传方法在哺乳动物细胞和体外进一步表征。我们建立了一个条件敲除小鼠模型，该模型缺乏位于经常缺失的染色体区域的一种假定的组蛋白甲基转移酶。基因敲除小鼠可构成慢性淋巴细胞白血病、哮喘和/或其他癌症或人类疾病的新模型。