Fig. 5

Estrogen-downregulated miRNAs target a network of genes enriched for biological processes relevant to sexual differentiation of the brain. a Limiting the number of targets per miRNA to no more than the top 25 (based on footscore), we interrogated a list of 1252 top genes targeted by estrogen-downregulated miRNAs for over-represented terms. ClueGO identified 7 clusters of 132 significantly enriched GO terms (Biological Processes). Cluster size in the pie graph is determined by the proportion of total GO term-gene annotations collapsed within a cluster. b The percentage of gene targets annotated by a clustered GO term. c Two GO terms, Gene Expression and System Development, seem particularly relevant to sexual differentiation of the brain. Five hundred and forty-five targets of estrogen-downregulated miRNAs were annotated with one or both of these GO terms and were used to generate a network. This network consists of estrogen-downregulated miRNAs and their target genes as nodes, and the miRNA-target connections as edges to allow the visualization of these interactions at a broad level. Genes annotated only with Gene Expression (n = 224) are colored blue, genes annotated only with System Development (n = 224) are colored red, and genes annotated with both terms (n = 156) are colored purple. Twenty-five percent of these genes are targeted by more than one miRNA. The size of individual gene nodes is proportional to the number of miRNAs targeting that gene, and ranges from one to four miRNAs/gene