Characterization of candidate histone methyltransferases

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通读转录本的组织特异性表达。通读转录物的主要部分可以添加修饰候选物之一的特异性的编码蛋白质结构域。目前正在编写这一工作的手稿。我们进行了几个酵母双杂交筛选，以确定蛋白质结合伙伴的假定组蛋白甲基转移酶。这些筛选产生了几个有趣的候选人，其特征在于进一步在哺乳动物细胞和体外的生化和遗传方法。我们已经产生了一个条件性基因敲除小鼠模型缺乏一个假定的组蛋白甲基转移酶位于一个经常删除的染色体区域。基因敲除小鼠可以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。

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.