Characterization of candidate histone methyltransferases

我们对两个候选组蛋白甲基转移酶在人类和小鼠组织中的转录进行了全面的分析，揭示了选择性剪接和通读转录产物的组织特异性表达。通读转录本的主要部分可以添加编码的蛋白质结构域来改变其中一个候选者的特异性。关于这部作品的手稿正在准备中。我们进行了几次酵母双杂交筛选，以确定可能的组蛋白甲基转移酶的蛋白结合伙伴。这些筛选产生了几个耐人寻味的候选基因，正在通过哺乳动物细胞和体外的生化和遗传方法进一步表征这些候选基因。我们已经建立了一个条件性基因敲除的小鼠模型，该模型缺少一个位于经常缺失的染色体区域的假定的组蛋白甲基转移酶。基因敲除的小鼠可能包括一种新的慢性淋巴细胞白血病、哮喘和/或其他癌症或人类疾病的模型。

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.