(A) Establishment of the NFR around promoters.
(B) KAP1 is tethered to gene promoters through direct interactions with the hypo-acetylated H4 tail. Specific promoter recognition may occur through yet unknown interactions with other TFs such as PIC subunits. See Discussion for complete details.
(C) Upon promoter binding, KAP1 directly stimulates Pol II recruitment and/or pausing and tethers 7SK-bound CDK9.
(D) In response to cognate signals (TGF-β), KAP1 recruits a pathway-specific TF (SMAD2) to select gene promoters thereby promoting CDK9 activation and Pol II pause-release.