Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation

被引:491
作者
Cui, Kairong [1 ]
Zang, Chongzhi [3 ]
Roh, Tae-Young [1 ]
Schones, Dustin E. [1 ]
Childs, Richard W. [2 ]
Peng, Weiqun [3 ]
Zhao, Keji [1 ]
机构
[1] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA
[3] George Washington Univ, Dept Phys, Washington, DC 20052 USA
基金
美国国家卫生研究院;
关键词
BETA-GLOBIN GENE; DNA METHYLATION; HISTONE MODIFICATIONS; PLURIPOTENT; EXPRESSION; BLOOD; MAPS; PROGENITORS; PROMOTERS; ENHANCERS;
D O I
10.1016/j.stem.2008.11.011
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 11 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.
引用
收藏
页码:80 / 93
页数:14
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