The SNF-2 related CBP-activating protein (SRCAP) regulates transcription through its interaction with the P-TEFb complex.

摘要

The P-TEFb complex is involved in the initiation of elongation during transcription. A pause in elongation is induced to allow capping of the nascent mRNA. P-TEFb overcomes this pausing by phosphorylating negative elongation factors (DSIF/NELF) bound to RNAPII, as well as RNA polymerase II. The active p-TEFb complex is composed of two proteins, CDK9 and Cyclin T1, and has been shown to interact with AF10-containing complexes. The transcription factor, AF10, is also known to interact with GAS41, a member of the SRCAP (SNF-2 related CBP activator protein) complex. The SRCAP complex, identified through its interaction with the histone acetyl transferase CBP, was shown to function as a co-activator for a number of transcription factors (CBP, AR, and GR). SRCAP also appears to regulate transcription by functioning as an ATP-dependent chromatin remodeling complex which replaces nucleosomal H2A with the histone variant H2A.Z. We have also found that SRCAP can activate transcription independent of this activity. We hypothesize that this transcriptional activity is due to the ability of the SRCAP complex to recruit p-TEFb to promoters. We have demonstrated that the interaction between SRCAP and AF10 has a synergistic effect on transcription and have obtained evidence that a decrease in SRCAP expression prevents the recruitment of CDK9 to the SP1 promoter. We therefore conceive that SRCAP may play a role in the initiation of elongation by recruiting the p-TEFb complex to promoters.