FIG 5.
JAK1 is required for the upregulation of isoform-specific STAT3 transcriptional targets and newly identified JAK1-responsive genes during mammary gland involution. The individual panels show the histograms of RNA-Seq data sets for selected genes, illustrating their expression levels and usage of exons in lactating and involuting mammary tissues from females with mammary gland-specific JAK1 knockout (MMTV-Cre Jak1fl/fl) and their wild-type controls (Jak1fl/fl). The box surrounding the second coding exon of Jak1 highlights the precise deletion of this exon in the conditional knockout mice. The beta-casein gene (Csn2) served as a control for a STAT5-responsive target gene that is downregulated during involution. Cd14 and Pik3r1 are examples of STAT3-responsive genes whose upregulation during involution is JAK1 dependent. c-Fos, Bmf, Bim, and Runx1 are newly identified targets of JAK1 signaling. Note the specific exon usage in Pik3r1, which encodes the alternative p50/p55 PI3 kinase regulatory subunit, and that expression of Runx1 during involution is driven by a shorter transcript known as isoform 3.