A model of TRIM28-mediated transcriptional regulation in Pol II promoter-proximal pausing and pause release. A transcriptional repressor TRIM28 is bound adjacent to the Pol II pausing site to stabilize the paused complex of Pol II. In a model paused gene, HSPA1B, heat-shock instantly recruits a gene-specific transcriptional activator, HSF1 to activate transcription. Upon transcriptional activation, TRIM28 is rapidly phosphorylated at S824. This phosphorylation is dependent on ATM and DNA-PK, critical DNA damage and repair kinases. This phosphorylation signaling appears important for Pol II pause release as blocking the function of these kinases interferes with Pol II progression into the 3′ terminus of HSPA1B.