A Cellular Factor for Regulation of Transcriptional Elongation by HIV TAT.
Abstract
Control of transcriptional elongation has been recognized as an important step in gene regulation, but mechanisms regulating the efficiency of elongation by RNA polymerase II have not been extensively studied. HIV-1 Tat has been used as a model system to study this process. It has been suggested that polymerase elongation can be modulated by association with general transcription elongation factors such as Elongin and TFIIF. Elongin has been identified as a Functional target of the von Hippel-Lindau tumor suppressor (VHL) protein. VHL binds tightly to Elongin and inhibits its activity. We have established a reconstituted transcription reaction that supports a Tat-specific and TAR-dependent activation of HIV-1 transcription. Using this system we have previously identified and purified a Tat-specific cofactor Tat-SF1. The reconstituted reaction also contains general elongation factors such as TFIIF and Elongin. We found that increasing the concentration of recombinant Elongin, but not TFIIF, in transcription reactions suppressed the degree of Tat activation by increasing the efficiency of elongation independent of Tat. Our data are consistent with a model that polymerase elongation in vitro may be limited by an Elongin-mediated process and Tat stimulates elongation by facilitating the interaction of Elongin with elongating polymerase complexes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA366658
Entities
People
- Qiang Zhou
Organizations
- Massachusetts Institute of Technology