HISTONES IN CELL DIFFERENTIATION & CARCINOGENESIS

我们的长期目标是阐明分子 基因差异表达的机制研究进展 特化的哺乳动物细胞，作为更好地理解 以及细胞缺陷引起的人类健康问题的治疗 分化，包括衰老和癌症。组织特异性 基因表达的模式反映在相应的模式中 不同的染色质构象。主要决定因素 染色质构象的主要成分是组蛋白。我们已经描述了一种 哺乳动物非等位一级结构变异体的数量 在不同情况下表达的组蛋白和 在成人组织中以不同的比例出现。为了 阐明每种组蛋白种类的特定功能及其 变种，我们在分子水平上定义了 和特定蛋白质-蛋白质和蛋白质-DNA的动力学 负责不同方面的相互作用 核小体结构和染色质构象。为了这个 目的：我们开发了蛋白质“足迹”分析方法。 同时衡量一种大的 的假定结合结构域中的特定结合点数 核心组蛋白。这些分析将被用来比较核小体 含有不同的变异体以及不同的染色质 功能状态。

Our long range goal is the elucidation of the molecular mechanisms responsible for the differential expression of genes in specialized mammalian cells, as a basis for better understanding and treatment of human health problems caused by defects in cell differentiation, including aging and cancer. The tissue-specific pattern of gene expression is reflected in a corresponding pattern of different chromatin conformation. The primary determinants of chromatin conformation are the histones. We have described a number of nonallelic primary structure variants of mammalian histones which are expressed under different circumstances and occur in different proportions in adult tissues. In order to elucidate the specific functions of each histone species and its variants, we are defining on the molecular level the properties and dynamics of specific protein-protein and protein-DNA interactions which are responsible for different aspects of nucleosome architecture and chromatin conformation. For this purpose we have developed protein "footprinting" assays which measure simultaneously the degree of protection of a large number of specific sites in the presumptive binding domains of the core histones. These assays will be used to compare nucleosomes containing different variants as well as chromatin in different functional states.