ESTROGEN RECEPTOR FUNCTION AND THE NUCLEAR MATRIX

越来越多的人认识到，核隔离是一种 核代谢的重要组成部分。 这一建议旨在 研究雌激素受体作为一个模型，以了解如何核 分室作用影响转录活性。 实现这一 目标，ER在不同激素水平下靶向的亚核结构域 将使用高分辨率显微镜研究条件， 与其他特异性亚核标记物的共定位研究 域. 雌激素受体内负责 与核基质的相互作用将由 产生缺失构建体和嵌合蛋白。 最后， ER与转录辅激活因子的相互作用， 将在核骨架背景下分析回归量，以确定 这些因子的亚核区室化如何调节基因 转录。

There is a growing awareness that nuclear compartmentation is an essential component of nuclear metabolism. This proposal is aimed at studying the estrogen receptor as a model to understand how nuclear comparmentation affects transcriptional activity. To achieve this goal, the subnuclear domains targeted by ER under varying hormonal conditions will studied using high resolution microscopy and colocalization studies with other markers of specific subnuclear domains. The regions within the estrogen receptor responsible for interaction with the nuclear matrix will be analyzed by the generation of deletion constructs and chimeric proteins. Finally, the interaction of ER with transcriptional coactivators and regressors will be analyzed in a nucleoskeletal context to determine how subnuclear compartmentation of these factors regulates gene transcription.