中文摘要
生物有机体的发育和细胞命运的决定受到信号分子、转录因子以及染色质等多因子的调控。在生理条件下,常常要求细胞能够对信号刺激作出迅速反应,调整和改变其染色质状态,调控基因表达。这要求信号通路和染色质之间要建立直接有效的联系。然而,信号通路和染色质的通讯机制还研究的很不充分。MGA(Max Gene Associate)是一个具有T-box和bHLHzip双功能域的转录因子和潜在的染色质调节子。我们发现MGA在细胞质与BMP通路I型受体特异地互作,调控BMP信号;在受到BMP信号诱导后,它能够迅速进入细胞核结合染色质。本课题,基于信号转导、染色质调节以及表观遗传理论,利用小鼠胚胎干细胞和斑马鱼为研究材料,通过构建MGA功能缺失的体外和在体研究模型,研究MGA穿梭于细胞核和胞质,调控BMP信号以及介导BMP信号和染色质直接通讯的机制。本课题将为研究信号转导和染色质直接通讯提供新的思路。
英文摘要
During development, at the cellular level signaling cascades initiated at cell surface relay a message through effector proteins,ultimately culminating in the nuclei,where chromatin regulators and transcriptional factors remodel the chromatin state and alter the gene expression. This event may be transient in nature, requiring the cells to response acutely to the developmental or environmental cues. How the signal transduction pathways directly communicate with chromatin to change its transcriptional state is not well-understood. Max Gene Associate (MGA) is a dual transcriptional factor containing T-box and bHLHzip domain, and a potential chromatin regulator. We found MGA associates with BMP type I receptor to reguate BMP, and enter into nuclei in response to BMP signal. We think MGA can shuttle between nuclei and cytoplasm, help to directly communicate BMP pathway and chromatin. We will utilize embryonic stem cell and zebrafish as in vitro and in vivo model, by constructing loss of function ES cells and zebrafish, to study the direct communication mechanism between BMP signal transduction and chromatin mediated by MGA.
