NUCLEAR STRUCTURE AND GENE EXPRESSION

我们的计划集中在核结构和核结构之间的相互关系 基因表达。它们在功能上与修饰的转录相关 对转化细胞和肿瘤细胞的控制。我们的工作假设是 支持细胞生长和表型的核结构参数 通过促进组织正常细胞和肿瘤细胞的性质 动态3中的染色体、基因、转录本和调节子 核建筑的维度背景。该中心的调查人员 马萨诸塞大学医学院在 建立概念和实验基础的多重 基因调控中的核组织参数。主要贡献 因为人们逐渐认识到原子核的结构成分 中介转录和基因转录本的处理已经被 由我们的计划项目调查人员之间的合作提供。这 团队方法提高了对核内贩运的理解 转录因子到支持基因表达的位点，调控 染色质重塑和染色体分离的结构和 核基质的功能性质和核基质的特性 功能新域。 我们致力于通过实验定义新的机制， 核形态改变与肿瘤细胞异常生长的关系 从亚核表示中的微扰角度来看， 核酸和基因调节蛋白的靶向。机制，由 哪种核结构整合了生理调节信号 支持基因表达的问题正在得到解决。我们正在调查后- 支持染色质重塑的组蛋白的翻译修饰 使转录因子可访问启动子元件，并 促进独立基因调控活动的协同作用 序列。对中心体组织的监管正在进行中 与有丝分裂器、染色体组装改变的关系 肿瘤细胞中的分离和易位以及非整倍体。我们的 目标是优化细胞、生化和 分子方法，以及体外和体内模型系统， 定义核体系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 与之相关的核组织。

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.