Latest Reply:
Hello again Hemant,
We encourage you to review the following section, "Possible Cooperation between Brd4 and Gene-Specific Transcriptional Activators in Recruitment of P-TEFb" in the article we cited in our latest response:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1594588/?tool=pubmed
At the end of this section, the authors state:
"Due to its ability to bind to P-TEFb, NF-κB may function in conjunction with Brd4 to recruit P-TEFb to the HIV-1 promoter. In addition, NF-κB can bring in a histone acetylase and cause histone acetylation, which in turn may further facilitate the recruitment of P-TEFb to the viral promoter by Brd4. These events can be envisioned to occur before the HIV-1 Tat protein is produced. After the initial round of transcription is completed and a small amount of Tat is synthesized, Tat clearly takes over and directly recruits P-TEFb to the TAR RNA element. This establishes a positive feed-forward loop, and optimal replication of the virus ensues."
Based on our review of this article, it appears as if BRD4-mediated activation of P-TEFb (in conjunction with NF-κB) plays a positive role in initiating HIV-1 transcription, which in turn promotes Tat expression. Once Tat is expressed, a positive feed-forward loop ensues, permitting enhanced transcription of the HIV-1 genome.
These events occur during the initiation of HIV-1 transcription (i.e., before Tat is produced). However, the positive role of BRD4 may change once Tat is produced. We encourage you to continue to review the literature on this fascinating topic. Best of luck to you!
Reply From:
Nature Education
Jul 25, 2010 01:47PM