NUCLEAR STRUCTURE AND GENE EXPRESSION

我们的计划是集中在核结构的相互关系， 基因表达。 在功能上与修饰的转录 转化细胞和肿瘤细胞中的对照。我们的假设是 核结构参数支持细胞生长和表型 正常细胞和肿瘤细胞的性质，通过促进组织 染色体、基因、转录本和调控因子在动态3- 核架构的维度背景。的调查人员 马萨诸塞州大学医学院一直致力于 建立多个概念和实验基础， 基因调控中的核组织参数。关键贡献 到逐渐认识到原子核的结构成分 介导的转录和基因转录物的加工已经被 由我们的项目研究人员合作提供。这 团队合作的方法促进了对核内贩运的理解， 转录因子到支持基因表达的位点， 染色质重塑和染色体分离，结构和 核基质的功能特性和 功能性新结构域。 我们致力于通过实验确定新的机制， 将核形态学变化与肿瘤细胞的异常生长联系起来 从亚核表象扰动的角度来看， 核酸和基因调节蛋白的靶向。机制 该核结构整合了生理调节信号， 支持基因表达。我们正在调查后- 支持染色质重塑的组蛋白翻译修饰 使启动子元件可接近转录因子， 促进独立基因调节活性的协同作用 序列的中心体组织的调节正在进行中， 与有丝分裂器、染色体装配改变的关系 分离和易位以及肿瘤细胞中的非整倍性。我们 目的是优化细胞、生化和 分子方法，连同体外和体内模型系统， 定义核结构支持保真度的机制， 基因表达。同样重要的是，我们将深入了解参数 核武器组织有联系。

Our program is focused on interrelationships of nuclear structure and gene expression. That are functionally linked to modified transcriptional control in transformed and tumor cells. Our working hypothesis is that parameters of nuclear structure support cell growth and phenotypic properties of normal and tumor cells by facilitating the organization of chromosomes, genes, transcripts and regulators within the dynamic 3- dimensional context of nuclear architecture. Investigators at the University of Massachusetts Medical School have been instrumental in establishing the conceptual and experimental basis for multiple parameters of nuclear organization in gene regulation. Key contributions to the emerging recognition that structural components of the nucleus mediate transcription and the processing of gene transcripts have been provided by collaborations among our program project investigators. This team approach has advanced understanding of intranuclear trafficking of transcription factors to sites that support gene expression, the regulation of chromatin remodeling and chromosome segregation, the structural and functional properties of the nuclear matrix and characteristics of functional novel domains. We are committed to experimentally defining novel mechanisms that relate changes in nuclear morphology to aberrant growth in tumor cells from the perspective of perturbations in the subnuclear representation and targeting of nucleic acid and gene regulator proteins. Mechanisms by which nuclear structure integrates physiological regulatory signals that support gene expression are being addressed. We are investigating post- translational modifications of histones that support chromatin remodeling to render promoter elements accessible to transcription factors and facilitate synergism of activities at independent gene regulatory sequences. Regulation of centrosome organization is being pursued in relation to altered assembly of the mitotic apparatus, chromosome segregation and translocation, as well as aneuploidy in tumor cells. Our objective is to optimize the combination of cellular, biochemical and molecular approaches, together with in vitro and in vivo model systems, to define mechanisms by which nuclear architecture supports fidelity of gene expression. Equally important, we will gain insight into parameters of nuclear organization that are associated.