Taube Ran, Lin Xin, Irwin Dan, Fujinaga Koh, Peterlin B Matija
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0703, USA.
Mol Cell Biol. 2002 Jan;22(1):321-31. doi: 10.1128/MCB.22.1.321-331.2002.
Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the positive transcription elongation factor b (P-TEFb). P-TEFb is composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK. The role of the C-terminal region of CycT1 and CycT2 remains unknown. In this report, we demonstrate that these sequences are essential for the activation of transcription by P-TEFb via DNA, i.e., when CycT1 is tethered upstream or downstream of promoters and coding sequences. A histidine-rich stretch, which is conserved between CycT1 and CycT2 in this region, bound the C-terminal domain of RNAPII. This binding was required for the subsequent expression of full-length transcripts from target genes. Thus, P-TEFb could mediate effects of enhancers on the elongation of transcription.
RNA聚合酶II（RNAPII）的转录延伸受正性转录延伸因子b（P-TEFb）调控。P-TEFb由细胞周期蛋白依赖性激酶9（Cdk9）和C型细胞周期蛋白T1（CycT1）、CycT2a、CycT2b或CycK组成。CycT1和CycT2 C末端区域的作用尚不清楚。在本报告中，我们证明这些序列对于P-TEFb通过DNA激活转录至关重要，即当CycT1锚定在启动子和编码序列的上游或下游时。在该区域CycT1和CycT2之间保守的富含组氨酸的片段与RNAPII的C末端结构域结合。这种结合是随后从靶基因表达全长转录本所必需的。因此，P-TEFb可以介导增强子对转录延伸的作用。
