Cui Kairong, Zang Chongzhi, Roh Tae-Young, Schones Dustin E, Childs Richard W, Peng Weiqun, Zhao Keji
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Cell Stem Cell. 2009 Jan 9;4(1):80-93. doi: 10.1016/j.stem.2008.11.011.
Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem cells/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1, and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these monomethylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1, and RNA polymerase II in HSCs/HPCs. Thus, our data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
组蛋白修饰与干细胞的维持和分化有关。我们分析了多能人类原代造血干细胞/祖细胞（HSCs/HPCs）分化为红细胞前体过程中全基因组范围内的基因表达和组蛋白修饰变化。我们的数据表明，H3K4me1、H3K9me1和H3K27me1在分化基因激活之前与增强子相关联，并与基础表达相关，这表明这些单甲基化参与了分化所需激活潜能的维持。此外，尽管HSCs/HPCs中与H3K4me3和H3K27me3都相关的大多数基因在分化后变得沉默并失去H3K4me3，但那些在分化后失去H3K27me3并被激活的基因在HSCs/HPCs中与H2A.Z、H3K4me1、H3K9me1、H4K20me1和RNA聚合酶II水平的增加相关。因此，我们的数据表明，分化过程中的基因表达变化是由HSC/HPC阶段存在的染色质修饰所编程的，并为增强子和启动子的鉴定提供了资源。
