Laboratory of Gene Regulation
Associate Professor Yutaka Hirose, Ph.D.
Assistant Professor Aki Tanaka, Ph.D.
After accomplishment of the human genome project, it has become obvious that we cannot understand the mechanisms of living activities by simply reading the whole gene sequences. For example, the body size and the extent of brain development of humans are quite different from those of mice although they both have almost identical 23,000 genes. Recently, it was also discovered with surprize that four certain transcription factors can induce differentiated cells to pluripotent stem cells. It has become obvious that these phenomena are caused by coordinative regulations of trascription and its closely related nuclear events. Our broad objectives are to elucidate the specific regulatory events that control such events, especially"the switch mechanisms of changing between transcription activation and repression"by using molecular biological, biochemical, and genetical approaches.
Main research projects
- 1. Studies on molecular mechanisms of transcription of eukaryotic genetic information
We are studying the transcriptional regulation mechanisms of RNA polymerase Ⅱ (Pol Ⅱ) by the general transcription factors and how the nuclear signals are transduced to Pol Ⅱ via the Mediator complex and are proceeded to transcription initiation, elongation and posttranscriptional regulations like RNA processing.
- 2. Studies on crosstalks between transcription and chromatin regulation primarily through the Mediator complex
Since the histone remodeling complex SWI/SNF, the transcriptional repressor polycomb complex, and the histone methylation enzymes were isolated as the Mediator interacting factors, we are studying the regulation mechenisms.
- 3. Studies on molecular mechanisms for the coordination of gene expression processes via the C-terminal domain of the RNA polymerase Ⅱ largest subunit
The C-terminal domain of the Pol Ⅱ largest subunit (CTD) is composed of tandem repeats of heptapeptide YSPTSPS and subjected to reversible phosphorylation during transcription cycle. The phosphorylated CTD plays critical roles in coordinating multiple nuclear processes by serving as a scaffold to recruit various proteins involved in transcription, chromatin modification, and RNA processing. We are studying on the molecular mechanisms for the coordination of gene expression processes by examining the roles of CTD kinases, phosphatases, and phosphorylated CTD binding factors in gene regulation.
