Fig. 2

Activity-driven promoter/enhancer interactions leading to transcriptional elongation. a. In the basal state, RNAPII appears in transcriptional factories (an incompletely described proteinaceous body that is depicted in the scheme as a large blue globe) (1). The C-terminus of RPB1 has 52 tandem repeats of the heptapeptide YSPTSPS that contains two Ser residues that are dynamically phosphorylated. S5 phosphorylation (in orange) and the presence of the transcriptional repressors NELF and DSIF impede transcriptional elongation and stall RNAPII at gene promoters (2). b. Upon neuronal activity, distal enhancer sequences interact with the promoter thanks to the action of cohesin (3), which together with acetylated TFIIIC-bound SINEs mediates the relocation of plasticity genes. Enhancer acetylation requires the action of lysine acetyltransferases (4), such as CBP and p300, subsequently promoting their relocation. Transcriptional machinery (elongating RNAPII, the Mediator complex and TFs) binds to the enhancer element in order to transcribe eRNAs (5) that in turn bind to NELF and release it from the promoter. Finally, the phosphorylations of RNAPII (at Ser2), NELF and DSIF (red circles) would trigger productive elongation (6). In addition, it has been recently proposed that Topo IIB-mediated DSBs (upstream of the TSS) eliminate the loop that separates the promoter from the transcription factory (7)