Structural Mechanisms Controlling Cell-Cycle Gene Expression

项目摘要 该研究项目旨在确定DREAM和Myb-MuvB（MMB）蛋白如何 复合物调节转录以控制细胞增殖。保守的MuvB 蛋白质复合物通过及时与细胞周期相关的基因结合， 特异性DNA结合转录因子，包括E2 F4-p130（DREAM）和Myb （MMB）。然而，五种蛋白MuvB复合物的生物化学功能尚不清楚。 我们提出并将测试MuvB如何与染色质相关联的新假设， DREAM如何通过稳定染色质结构抑制转录，以及Myb如何 通过与MuvB结合激活基因表达。这些研究将提供 关于细胞周期是如何控制的基本新见解，并将揭示一个新的 转录因子直接调节基因表达的新机制 通过核小体定位。

Project summary This research project aims to determine how the DREAM and Myb-MuvB (MMB) protein complexes regulate transcription to control cell proliferation. The conserved MuvB protein complex either represses or activates cell-cycle genes by timely association with specific DNA-binding transcription factors including E2F4-p130 (DREAM) and Myb (MMB). However, the biochemical function of the five protein MuvB complex is unknown. We propose and will test novel hypotheses for how MuvB associates with chromatin, how DREAM inhibits transcription by stabilizing chromatin structure, and how Myb activates gene expression through its association with MuvB. These studies will provide fundamental new insights regarding how the cell cycle is controlled and will uncover a novel mechanism for how transcription factors directly modulate gene expression through nucleosome positioning.