Dual Roles Of AFF1 In Regulating Pause Release Of RNA Polymerase ?

The regulation of RNA polymerase?(Pol II)pause and release is a critical step point during transcriptional elongation in metazoan cells.After transcription initiation,Pol II can transcribe about 20-60 bases and then pause at the promoter-proximal region in the effect of 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole(DRB)sensitivity-inducing factor DSIF and negative transcription factors NELF.In response to developmental signals or environmental stress,the positive transcription factor P-TEFb enters and phosphorylates Pol II,DSIF and NELF,resulting in the release of Pol II from the pause site into the elongation state.The regulation of Pol II pause and release is critical for the rapid expression of genes which mis-regulation may lead to many diseases.However,the roles of key regulatory factors in this process is not very explicit and needs to be further investigated.Here,we used ChIP-seq,RNA-seq and biological analysis revealed that AFF1,a member of the ALF family,plays dual roles in regulating the pause and release of promoter-proximal paused Pol II.Specifically,the super elongation complex(SEC)component AFF1,but not another ALF family member AFF4,promotes Pol II release from pausing sites at highly transcribed genes.On the other hand,AFF1 can bind to enhancers and function together with TRIM28,in inhibition of the release of Pol II via preventing the accumulation of SEC on nearest genes.Therefore,our data reveal that AFF1 plays different roles in transcriptional regulation when combined with different proteins: one is the classical transcriptional activation mode which depends on SEC;the other is the nonclassical pattern as mentioned above,suppressing the Pol II release via enhancer,which has novel and important significance in the research of transcriptional regulation.