We are studying the mechanisms and factors that control transcriptional elongation and how this control affects HIV replication, latency activation and cancer progression.
The elongation phase of RNA polymerase (Pol) II transcription is widely used to regulate the expression of metazoan genes, especially those for cell growth, renewal and differentiation. Composed of CDK9 and cyclin T (CycT), the positive transcription elongation factor b (P-TEFb) is one of the most important factors that promote the transition of Pol II from promoter-proximal pausing into productive elongation. P-TEFb acts by phosphorylating the Pol II C-terminal domain (CTD) and negative elongation factors to antagonize the latter’s inhibitory effects. This leads to the synthesis of full-length RNA transcripts and the coupling of transcription with pre-mRNA processing.
The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation. [Li Z, Guo J, Wu Y, Zhou Q. (2012) Nucleic Acids Res.]
The ubiquitin ligase Siah1 controls ELL2 stability and formation of Super Elongation Complexes (SECs) to modulate gene transcription. [M. Liu, J. Hsu, C. Chan, Z. Li, and Q. Zhou (2012) Mol Cell, 46, 325-334]
RNA Polymerase II elongation control. [Q. Zhou, T. Li, and D.H. Price (2012) Annu. Rev. Biochem. 81, 119-143]
Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin. [N. He, C.K. Chan, B. Sobhian, Y. Xue, M. Liu, M. Benkirane, and Q. Zhou (2011) Proc. Natl. Acad. Sci. USA.108, 14719-14720]
The control of HIV transcription: Keeping RNA Polymerase II on track. [M. Ott, M. Geyer, and Q. Zhou (2011) Cell Host & Microbe 10, 426-435]
HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. [N. He, M. Liu, J. Hsu, Y. Xue, S. Chou, A. Burlingame, N.J. Krogan, T. Alber, and Q. Zhou (2010). Mol Cell 38, 428-438]