Tyrosine 1–phosphorylated RNA polymerase II transcribes PROMPTs to facilitate proximal promoter pausing and induce global transcriptional repression in response to DNA damage

IR-induced DNA damage leads to global down-regulation of protein-coding genes (PCGs). (A) mNET-seq experimental design shows the sample preparation of irradiated and nonirradiated U2OS cells from which Y1P, S2P, and S5P RNA Pol II were precipitated for mNET-seq. (B) Venn diagram of significantly down-regulated (Padj < 0.05, log₂FC < −0.1) PCGs based on read coverage across the gene body (GB) from Y1P, S2P, and S5P samples after IR. (C) Volcano plots of differentially expressed PCGs based on read coverage across GB from Y1P samples upon IR. (D) Volcano plots of differentially expressed PCGs based on read coverage across GB from S2P samples upon IR. (E) Volcano plots of differentially expressed PCGs based on read coverage across GB from S5P samples upon IR. (F) GO enrichment of significantly down-regulated genes across Y1P, S2P, and S5P samples upon IR. (G) IGV profile of mNET-seq signal across a representative down-regulated gene, MT-CYB.