Biomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Oncogene. 2014 Mar 6;33(10):1207-17. doi: 10.1038/onc.2013.87. Epub 2013 Mar 18.
Altered expression or activity of histone lysine methylases and demethylases in cancer lead to aberrant chromatin modification patterns, which contribute to uncontrolled cell proliferation via cancer-specific deregulation of gene expression programs or the induction of genome instability. Several transcription factors that regulate growth-associated genes undergo lysine methylation, expanding the repertoire of regulatory targets modulated by histone-methylating enzymes during tumorigenesis. In certain specific tumor types or specific physiological conditions, these enzymes may trigger chromatin structure and/or transcription factor activity changes that result in opposite effects on cancer initiation or progression. The mechanisms of such context-specific dual functions and those involved in the crosstalk between factor and histone modifications are subject to extensive research, which is beginning to shed light into this novel level of complexity of cancer-related epigenetic pathways.
在癌症中，组蛋白赖氨酸甲基转移酶和去甲基化酶的表达或活性改变导致染色质修饰模式异常，这通过肿瘤特异性的基因表达程序失控或基因组不稳定性的诱导，导致不受控制的细胞增殖。几种调节生长相关基因的转录因子发生赖氨酸甲基化，扩大了组蛋白甲基化酶在肿瘤发生过程中调节的调控靶点谱。在某些特定的肿瘤类型或特定的生理条件下，这些酶可能会引发染色质结构和/或转录因子活性的变化，从而对癌症的起始或进展产生相反的影响。这种特定于上下文的双重功能的机制以及因子和组蛋白修饰之间的串扰机制都在广泛的研究中，这开始揭示了与癌症相关的表观遗传途径的这种新的复杂性水平。
