The role of DOT1L in the maintenance of leukemia gene expression.
The role of DOT1L in the maintenance of leukemia gene expression.
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DOI：
10.1016/j.gde.2016.03.015
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发表时间：
2016-02
影响因子：
4
通讯作者：
Xi Wang;Chun-Wei Chen;S. Armstrong
中科院分区：
文献类型：
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作者：
Xi Wang;Chun-Wei Chen;S. Armstrong
基于染色质的（表观遗传）机制已被证明在肿瘤发生和发展过程中的基因表达调控中起重要作用。小鼠模型表明甲基转移酶DOT1L是MLL重排白血病的潜在治疗靶点。表观基因组分析表明MLL融合靶向基因上的异常H3K79me2模式，但这种表观遗传依赖性的分子机制尚未得到很好的理解。在这篇综述中，我们将讨论在理解DOT1L在维持基因表达的表观遗传机制方面的最新进展。我们将强调染色质靶向DOT1L通过其辅因子的结构基础和DOT1L在排斥白血病发展过程中的转录抑制复合物的作用。
Chromatin based (Epigenetic) mechanisms have been shown to play important roles in the regulation of gene expression during tumorigenesis and development. Mouse modeling suggests the methyltransferase DOT1L as a potential therapeutic target for MLL-rearranged leukemia. Epigenomic profiling indicates an abnormal H3K79me2 pattern on MLL-fusion targeted genes, but the molecular mechanism underlying this epigenetic dependency is not well understood. In this review, we will discuss recent advances in understanding the epigenetic mechanisms governed by DOT1L in the maintenance of gene expression. We will highlight the structural basis of chromatin targeting of DOT1L through its cofactors and the role of DOT1L in repelling transcription repressive complexes during leukemia development.