Fig. 2

Estrogen regulation of clustered miRNA genes on chromosome 12. a Twenty-four sex-biased miRNAs are encoded in three clusters (designated 12A, 12B, and 12C) within a ~ 175 kb region of chromosome 12 [mm9 chr12 110810200–110986170 (+)]. These 24 miRNAs constitute 44% of the miRNAs located in these clusters, which is well above the background rate of 16% of the total clustered miRNAs we assayed that were sex-biased. b This effect is even more impressive when focusing on 12A and 12B. Nine of 16 miRNAs in 12A and 12B were estrogen-responsive (colored red), and an additional four were characterized as “other” (colored blue). Together, 81% of the miRNAs in these two clusters are reduced in control males relative to females, suggesting the miRNA genes in this locus are co-regulated. Ten transcription start sites (TSSs) have been mapped just to the 12A locus; thus, it is unlikely that they are regulated from a shared promoter. Instead, it appears that estrogen could be affecting the expression of these miRNAs through the epigenetic regulation of the entire locus. miRNA clusters were defined by MetaMirCluster using a maximum inter-miRNA distance of 10 kb [34]. TSS mapping data was produced by the FANTOM5 Consortium and obtained as a UCSC Genome Browser public track (FANTOM5 TSS peaks [robust]) [35]