Regulation of microRNA expression and abundance during lymphopoiesis.
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.
Kuchen
Stefan
S
Genomics and Immunity, NIAMS, NIH, Bethesda, MD 20892, USA.
Resch
Wolfgang
W
Yamane
Arito
A
Kuo
Nan
N
Li
Zhiyu
Z
Chakraborty
Tirtha
T
Wei
Lai
L
Laurence
Arian
A
Yasuda
Tomoharu
T
Peng
Siying
S
Hu-Li
Jane
J
Lu
Kristina
K
Dubois
Wendy
W
Kitamura
Yoshiaki
Y
Charles
Nicolas
N
Sun
Hong-wei
HW
Muljo
Stefan
S
Schwartzberg
Pamela L
PL
Paul
William E
WE
O'Shea
John
J
Rajewsky
Klaus
K
Casellas
Rafael
R
D000818:Animals; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs