Endoh Masaki, Zhu Wenyan, Hasegawa Jun, Watanabe Hajime, Kim Dong-Ki, Aida Masatoshi, Inukai Naoto, Narita Takashi, Yamada Tomoko, Furuya Akiko, Sato Hiroe, Yamaguchi Yuki, Mandal Subhrangsu S, Reinberg Danny, Wada Tadashi, Handa Hiroshi
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan.
Mol Cell Biol. 2004 Apr;24(8):3324-36. doi: 10.1128/MCB.24.8.3324-3336.2004.
Recent studies have suggested that Spt6 participates in the regulation of transcription by RNA polymerase II (RNAPII). However, its underlying mechanism remains largely unknown. One possibility, which is supported by genetic and biochemical studies of Saccharomyces cerevisiae, is that Spt6 affects chromatin structure. Alternatively, Spt6 directly controls transcription by binding to the transcription machinery. In this study, we establish that human Spt6 (hSpt6) is a classic transcription elongation factor that enhances the rate of RNAPII elongation. hSpt6 is capable of stimulating transcription elongation both individually and in concert with DRB sensitivity-inducing factor (DSIF), comprising human Spt5 and human Spt4. We also provide evidence showing that hSpt6 interacts with RNAPII and DSIF in human cells. Thus, in vivo, hSpt6 may regulate multiple steps of mRNA synthesis through its interaction with histones, elongating RNAPII, and possibly other components of the transcription machinery.
最近的研究表明，Spt6参与RNA聚合酶II（RNAPII）介导的转录调控。然而，其潜在机制仍 largely未知。一种可能性是Spt6影响染色质结构，这一观点得到了酿酒酵母的遗传学和生化研究的支持。另一种可能性是，Spt6通过与转录机制结合直接控制转录。在本研究中，我们证实人类Spt6（hSpt6）是一种经典的转录延伸因子，可提高RNAPII的延伸速率。hSpt6既能单独刺激转录延伸，也能与由人类Spt5和人类Spt4组成的DRB敏感性诱导因子（DSIF）协同发挥作用。我们还提供证据表明hSpt6在人类细胞中与RNAPII和DSIF相互作用。因此，在体内，hSpt6可能通过与组蛋白、延伸中的RNAPII以及转录机制的其他可能组分相互作用来调控mRNA合成的多个步骤。
