title: Regulation of microRNA expression and abundance during lymphopoiesis.
abstract: 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.
authors.affiliation: Genomics and Immunity, NIAMS, NIH, Bethesda, MD 20892, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuchen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Nan
authors.initials: N
authors.lastname: Kuo
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Tirtha
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yasuda
authors.forename: Siying
authors.initials: S
authors.lastname: Peng
authors.forename: Jane
authors.initials: J
authors.lastname: Hu-Li
authors.forename: Kristina
authors.initials: K
authors.lastname: Lu
authors.forename: Wendy
authors.initials: W
authors.lastname: Dubois
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charles
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Sun
authors.forename: Stefan
authors.initials: S
authors.lastname: Muljo
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: John
authors.initials: J
authors.lastname: O'Shea
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
mesh_terms: 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
chemical_list: D035683:MicroRNAs