Update information. RNA polymerase II drives mRNA gene expression, yet our understanding of global Pol II repression is limited. Using auxin-inducible degron, we degraded Pol II's RPB1 subunit in mESCs, resulting in global repression, yet certain genes exhibited increased RNA levels post-degradation. These genes are associated with GPCR ligand binding and are characterized by being less paused and comprising polycomb-bound short genes. RPB1 degradation globally increased KDM6B binding, which was insufficient to explain specific gene activation. In contrast, RPB2 degradation repressed nearly all genes, accompanied by decreased H3K9me3 and SUV39H1 occupancy. We observed a specific increase in serine 2 phosphorylated Pol II at Pol II degradation-upregulated genes, indicating their resistance to degradation. Additionally, a-amanitin or UV treatment resulted in RPB1 degradation and global gene repression, unveiling subsets of upregulated genes. Our findings highlight the activation of signaling genes as a potential mechanism for cells to counter global transcription shutdown during stress.