School of Life Sciences, Jilin University, Changchun 130012, China.
School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
Molecules. 2020 Jan 29;25(3):578. doi: 10.3390/molecules25030578.
Epigenetic modifications (or epigenetic tags) on DNA and histones not only alter the chromatin structure, but also provide a recognition platform for subsequent protein recruitment and enable them to acquire executive instructions to carry out specific intracellular biological processes. In cells, different epigenetic-tags on DNA and histones are often recognized by the specific domains in proteins (readers), such as bromodomain (BRD), chromodomain (CHD), plant homeodomain (PHD), Tudor domain, Pro-Trp-Trp-Pro (PWWP) domain and malignant brain tumor (MBT) domain. Recent accumulating data reveal that abnormal intracellular histone modifications (histone marks) caused by tumors can be modulated by small molecule-mediated changes in the activity of the above domains, suggesting that small molecules targeting histone-mark reader domains may be the trend of new anticancer drug development. Here, we summarize the protein domains involved in histone-mark recognition, and introduce recent research findings about small molecules targeting histone-mark readers in cancer therapy.
DNA 和组蛋白上的表观遗传修饰（或表观遗传标记）不仅改变了染色质结构，还为随后的蛋白质募集提供了一个识别平台，并使它们能够获得执行指令，以执行特定的细胞内生物过程。在细胞中，DNA 和组蛋白上的不同表观遗传标记通常被蛋白质（读取器）中的特定结构域识别，如溴结构域（BRD）、色氨酸-丝氨酸-丝氨酸（CHD）、植物同源结构域（PHD）、Tudor 结构域、脯氨酸-色氨酸-色氨酸-脯氨酸（PWWP）结构域和恶性脑肿瘤（MBT）结构域。最近积累的数据表明，肿瘤引起的细胞内组蛋白修饰（组蛋白标记）异常可以通过小分子介导的上述结构域活性变化来调节，这表明针对组蛋白标记读取器结构域的小分子可能是新抗癌药物开发的趋势。在这里，我们总结了涉及组蛋白标记识别的蛋白质结构域，并介绍了针对癌症治疗中组蛋白标记读取器的小分子的最新研究发现。
