组蛋白去甲基化酶 UTX 能够实现 RB 依赖性细胞命运控制。
The histone demethylase UTX enables RB-dependent cell fate control.
机构信息
Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
出版信息
Genes Dev. 2010 Feb 15;24(4):327-32. doi: 10.1101/gad.1882610. Epub 2010 Feb 1.
Abstract
Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis of UTX and associated histone modifications reveals distinct classes of UTX target genes, including genes encoding Retinoblastoma (RB)-binding proteins. UTX removes H3K27me3 and maintains expression of several RB-binding proteins, enabling cell cycle arrest. Genetic interactions in mammalian cells and Caenorhabditis elegans show that UTX regulates cell fates via RB-dependent pathways. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control.
摘要
组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）对于细胞命运调控至关重要。H3K27me3 去甲基化酶 UTX 在发育和肿瘤抑制中发挥作用，但具体机制尚不清楚。本研究通过对 UTX 及其相关组蛋白修饰的全基因组染色质占有率分析，揭示了 UTX 靶基因的不同类别，包括编码视网膜母细胞瘤（RB）结合蛋白的基因。UTX 可去除 H3K27me3，并维持多个 RB 结合蛋白的表达，从而导致细胞周期停滞。哺乳动物细胞和秀丽隐杆线虫中的遗传相互作用表明，UTX 通过 RB 依赖性途径调节细胞命运。因此，UTX 定义了一种进化保守的机制，可协调 RB 网络在细胞命运控制中的转录。
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