作　　者： ; ; ; ; ;

机构地区： 北京大学深圳医院

出　　处： 《中国生物化学与分子生物学报》 2011年第8期706-711,共6页

摘　　要： 组蛋白甲基化是一种重要的表观遗传学修饰,在基因表达调节方面发挥着重要的作用.组蛋白H3赖氨酸27三甲基化(H3K27me3)是一种抑制性组蛋白标记,可被去甲基化酶UTX和JMJD3催化而移去甲基.UTX和JMJD3通过激活HOX基因而参与细胞分化和多能细胞抑制过程.在多种肿瘤中检测到UTX和JMJD3突变或表达下降,同时多种基因启动子区H3K27me3含量增多.UTX和JMJD3均被看作肿瘤抑制基因,其中UTX调节了RB依赖的细胞命运控制,而JMJD3通过激活INK4b-ARF-INK4a位点而参与了癌基因诱导的衰老.组蛋白H3K27去甲基化酶与肿瘤发生的研究使我们对癌症发展过程有了更好的理解,同时也为癌症诊断和治疗提供了新靶点. Histone methylation is an important epigenetic modification and plays vital roles in the regulation of gene expression.Histone 3 lysine 27 tri-methylation（H3K27me3） is a repressive histone mark and can be catalyzed the removal of methyl group by H3K27 demethylases UTX and JMJD3.Both UTX and JMJD3 are involved for cell differentiation and multipotent cell inhibition through catalysing the demethylation of H3K27me3 on the HOX genes locus and HOX activation.It was discovered that UTX and JMJD3 were mutated or down-regulated in many kinds of cancer,while the content of H3K27me3 in the promoters of many differentiation genes was increased.Both UTX and JMJD3 are considered as tumor suppressors.UTX regulates RB-dependent cell fate control,and JMJD3 participates in oncogene induced senescence by the activation of the INK4b-ARF-INK4a locus.The reseaches on histone H3K27 demethylases and tumorigenesis provide us a better understanding of the development of cancer and a novel target of cancer diagnosis and treatment.

关 键 词： 组蛋白 去甲基化酶 肿瘤发生 表观遗传学

领　　域： [生物学]