Zhang Lu-Qiang, Fan Guo-Liang, Liu Jun-Jie, Liu Li, Li Qian-Zhong, Lin Hao
Laboratory of Theoretical Biophysics, School of Physical Science and Technology, Inner Mongolia University, Hohhot, China.
The Research Center for Laboratory Animal Science, College of Life Sciences, Inner Mongolia University, Hohhot, China.
Front Cell Dev Biol. 2021 Jan 12;8:621578. doi: 10.3389/fcell.2020.621578. eCollection 2020.
Chronic myelogenous leukemia (CML) is a type of cancer with a series of characteristics that make it particularly suitable for observations on leukemogenesis. Research have exhibited that the occurrence and progression of CML are associated with the dynamic alterations of histone modification (HM) patterns. In this study, we analyze the distribution patterns of 11 HM signals and calculate the signal changes of these HMs in CML cell lines as compared with that in normal cell lines. Meanwhile, the impacts of HM signal changes on expression level changes of CML-related genes are investigated. Based on the alterations of HM signals between CML and normal cell lines, the up- and down-regulated genes are predicted by the random forest algorithm to identify the key HMs and their regulatory regions. Research show that H3K79me2, H3K36me3, and H3K27ac are key HMs to expression level changes of CML-related genes in leukemogenesis. Especially H3K79me2 and H3K36me3 perform their important functions in all 100 bins studied. Our research reveals that H3K79me2 and H3K36me3 may be the core HMs for the clinical treatment of CML.
慢性粒细胞白血病（CML）是一种具有一系列特征的癌症，使其特别适合用于白血病发生的观察研究。研究表明，CML的发生和进展与组蛋白修饰（HM）模式的动态变化有关。在本研究中，我们分析了11种HM信号的分布模式，并计算了CML细胞系中这些HM与正常细胞系相比的信号变化。同时，研究了HM信号变化对CML相关基因表达水平变化的影响。基于CML与正常细胞系之间HM信号的变化，通过随机森林算法预测上调和下调基因，以识别关键的HM及其调控区域。研究表明，H3K79me2、H3K36me3和H3K27ac是白血病发生过程中CML相关基因表达水平变化的关键HM。特别是H3K79me2和H3K36me3在所研究的所有100个区间中都发挥着重要作用。我们的研究表明，H3K79me2和H3K36me3可能是CML临床治疗的核心HM。
