Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation.
Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation.
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DOI：
10.1016/j.stem.2008.11.011
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发表时间：
2009-01-09
期刊：
影响因子：
23.9
通讯作者：
Zhao K
中科院分区：
文献类型：
--
作者：
Cui K;Zang C;Roh TY;Schones DE;Childs RW;Peng W;Zhao K
组蛋白修饰与干细胞维持和分化有关。我们已经在分化的人类原代造血干/祖细胞（HSC/HPC）中分化了基因表达和组蛋白修饰的全基因组变化。我们的数据表明，H3K4ME1，H3K9ME1和H3K27ME1在激活之前与分化基因的增强子相关，并与基础表达相关，这表明这些单甲基化与分化所需的激活电位所需的激活电位有关。此外，尽管HSC/HPC中与H3K4me3和H3K27me3的大多数基因在分化后变得沉默并失去H3K4me3，但那些损失H3K27ME3并在差异后激活的人与H2A.Z，H2A.Z，H3K4ME1，H3K9ME1，H4K9ME1，H4K20ME的水平增加有关和RNA聚合酶II HSCS/HPCS。因此，我们的结果表明，分化过程中的基因表达变化是通过HSC/HPC阶段存在的染色质修饰来编程的，我们为增强子和启动子识别提供了资源。
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/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 mono-methylations 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 results suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and we provide a resource for enhancer and promoter identification.
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