Regulation of MicroRNA Expression and Abundance during Lymphopoiesis

被引:283
作者
Kuchen, Stefan
Resch, Wolfgang [1 ]
Yamane, Arito
Kuo, Nan
Li, Zhiyu
Chakraborty, Tirtha [2 ,3 ]
Wei, Lai
Laurence, Arian
Yasuda, Tomoharu [2 ,3 ]
Peng, Siying [2 ,3 ]
Hu-Li, Jane [4 ]
Lu, Kristina [5 ]
Dubois, Wendy [6 ]
Kitamura, Yoshiaki [1 ]
Charles, Nicolas [1 ]
Sun, Hong-wei
Muljo, Stefan [4 ]
Schwartzberg, Pamela L. [5 ]
Paul, William E. [4 ]
O'Shea, John
Rajewsky, Klaus [2 ,3 ]
Casellas, Rafael [7 ]
机构
[1] NIAMS, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA
[2] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[4] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
[5] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA
[6] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA
[7] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
POSTTRANSCRIPTIONAL REGULATION; CELL DIFFERENTIATION; STEM-CELLS; SMALL RNAS; IDENTIFICATION; BIOGENESIS; PATTERNS; DICER; SPECIFICITY; ABSENCE;
D O I
10.1016/j.immuni.2010.05.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within the context of the transcriptome and epigenome. We show that lymphocyte-specific miRNAs are either tightly controlled by polycomb group-mediated H3K27me3 or maintained in a semi-activated epigenetic state prior to full expression. Because of miRNA biogenesis, the cellular concentration of mature miRNAs does not typically reflect transcriptional changes. However, we uncover a subset of miRNAs for which abundance is dictated by miRNA gene expression. We confirm that concentration of 5p and 3p miRNA strands depends largely on free energy properties of miRNA duplexes. Unexpectedly, we also find that miRNA strand accumulation can be developmentally regulated. Our data provide a comprehensive map of immunity's microRNome and reveal the underlying epigenetic and transcriptional forces that shape miRNA homeostasis.
引用
收藏
页码:828 / 839
页数:12
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