Figure 1.
Postnatal sex-biased gonadal gene expression, chromatin accessibility, transcription factor binding and chromatin architecture. (A) Plot of RNA-seq data comparing expression differences between postnatal granulosa and Sertoli cells isolated at P23-29 and P7, respectively. mRNAs with significant expression differences are colored red (granulosa-biased) or blue (Sertoli-biased). X axis indicates the log2 fold change in expression between the cell types and Y axis corresponds to the –log10 of the Benjamini–Hochberg corrected P-value such that genes with greater statistical significance are higher on this plot. (B, C) Plots of ATAC-seq data comparing chromatin accessibility between postnatal granulosa and Sertoli cells. Genomic regions that had a two-fold change in accessibility, a Benjamini-Hochberg adjusted P-value <0.05 and a peak-width normalized FPKM value >2.5, or constitutive regions called in both cell types with a fold-change less than 1.25 and an FPKM >2.5 in both cell types are shown. Axes represent the fold-change and significance as in (A). Granulosa-biased differentially accessible regions (DARs) have negative log2 values and Sertoli-biased DARs have positive values (X axis). In (B), genomic regions within 5 kilobases (kb) or between 5 and 100 kb of a sex-biased gene are shown in the upper or lower panels respectively. In (C), colors identify DARs bound by DMRT1 and/or SOX9 in Sertoli cells and FOXL2 and ESR2 in the ovary, based on ChIP-seq analysis. DARs labeled with ‡ and † correspond to the peaks labeled in panel D. (D) Genomic analysis of regions near Sox9 (left), Esr2 (center), and Foxl2 (right), showing sex-biased ATAC-seq accessibility and transcription factor ChIP-seq. The scale shown at right of each track indicates the number of reads per million reads sequenced for the full height of the track. The locations of DARs and ChIP peaks are indicated by a line underneath each peak for visibility. Prenatal ChIP-seq and ATAC-seq data are from Krentz et al. (42) and Garcia-Moreno et al. (6) respectively. Note that fetal ATAC-seq signal around TESCO in both sexes (labeled with *) is thought to derive in part from reporter transgene used in cell sorting (38). Coordinates in the GRCm38 genome build are shown at the top of each panel and gene models are diagrammed at bottom.
