TY - JOUR
T1 - Regulation of MicroRNA expression and abundance during lymphopoiesis
AU - Kuchen, Stefan
AU - Resch, Wolfgang
AU - Yamane, Arito
AU - Kuo, Nan
AU - Li, Zhiyu
AU - Chakraborty, Tirtha
AU - Wei, Lai
AU - Laurence, Arian
AU - Yasuda, Tomoharu
AU - Peng, Siying
AU - Hu-Li, Jane
AU - Lu, Kristina
AU - Dubois, Wendy
AU - Kitamura, Yoshiaki
AU - Charles, Nicolas
AU - Sun, Hong wei
AU - Muljo, Stefan
AU - Schwartzberg, Pamela L.
AU - Paul, William E.
AU - O'Shea, John
AU - Rajewsky, Klaus
AU - Casellas, Rafael
N1 - Funding Information:
We thank members of the Casellas lab for discussions; J. Newman and R. Young for mouse ESCs; J. Simone for cell sorting; G. Gutierrez for technical assistance with the genome analyzer; B. Wold for the mRNA-seq protocol; and L. Naldini for the LV-SFFV lentiviral vector. This work was supported in part by the Intramural Research Program of NIAMS-NIH. S. K. was supported by the Swiss Foundation for Grants in Biology and Medicine.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2010.05.009
DO - 10.1016/j.immuni.2010.05.009
M3 - Article
C2 - 20605486
AN - SCOPUS:77953915915
SN - 1074-7613
VL - 32
SP - 828
EP - 839
JO - Immunity
JF - Immunity
IS - 6
ER -
