Table 2. Mechanisms directing the anchoring and regulation of canonical 7SK snRNP on chromatin.
| Anchoring 7SK snRNP to chromatin | ||
| Chromatin adaptor factors (Ch-AFs) | Factor | Mode of action |
| Repressive chromatin mark | H4R3me2(s) | Binds first half of 7SK to recruit 7SK snRNP to A-PEs. |
| Transcription regulator | KAP1 (TRIM28 or TIF1β) | Binds LARP7 to recruit 7SK snRNP to promoters. |
| Non-histone chromatin protein | HMGA1 | Binds CTIP2 and SL2 of 7SK to recruit 7SK snRNP to promoters. |
| Releasing P-TEFb from 7SK snRNP | ||
| Signal transduction pathways | Factor | Mode of action |
| T-cell receptor signaling | PKCθ | Phosphorylates HEXIM1 Ser158 to prevent 7SK binding. |
| ERK | ERK-dependent kinase phosphorylates HEXIM1 Tyr271 and Tyr274 to prevent CycT1/P-TEFb binding. | |
| PI3K/Akt signaling | Akt | Phosphorylates HEXIM1 Ser270 and Thr278 to prevent CycT1/P-TEFb binding. |
| Ca2+-calmodulin-PP2B signaling | PP2B + PP1α | PP1α dephosphorylates P-Thr186 in Cdk9 after PP2B remodels 7SK snRNP. |
| Ca2+-dependent calpain 2 activation | Calpain 2 | Cleaves MePCE to destabilize core 7SK snRNP. |
| P-TEFb release factors (P-REFs) | Factor | Mode of action |
| HIV-1 transactivator of transcription | Tat | Binds the distal part in SL1 of 7SK and CycT1 to dislodge HEXIM1; recruits PPM1G for P-Thr186 Cdk9 dephosphorylation. |
| HTLV-1 transactivator of transcription | Tax | Binds CycT1 to dislodge HEXIM1. |
| Inducible transcription factor | NF-κB | Recruits PPM1G for P-Thr186 Cdk9 dephosphorylation. |
| Splicing and transcription regulator | SRSF2 | Binds SL3 of 7SK and nascent RNA to trigger the release. |
| DEAD-box RNA helicase | DDX21 | Binds SL3 of 7SK and changes conformation of 7SK. |
| hnRNPs and RNA helicase A | hnRNP A1, A2/B1, Q, R and RNA helicase A | Bind SL3 of 7SK to enable the subsequent release. |
| Histone demethylase | JMJD6 | Demethylates H4R3me2(s) and 7SK cap at A-PEs. |
| Histone acetyltransferase | p300 | Acetylates CycT1 to dislodge HEXIM1. |
Table summarizes principal ways by which 7SK snRNP is anchored to chromatin and by which P-TEFb is released from 7SK snRNP for promoting Pol II escape from pausing. For each factor, the mode of action is provided. The acronym SL stands for stem loop in 7SK.