ERYTHROID-SPECIFIC GENE REGULATION

描述：（改编自摘要）研究的长期目标是 了解组织和发育特异性的基因调控 在红系细胞中表达。 调查人员集中在 B珠蛋白基因座的基因调控作为红系特异性 基因表达。 这些基因的调控依赖于转录 仅限于红系细胞或与红系细胞密切相关的细胞的因子 谱系，并在一个有组织的染色质结构所决定的形成 在一个称为LCR或基因座控制的区域内， 地区 调查发现了一个新的cis 参与人B珠蛋白基因表达的元件。 此元素 赋予强的增强子活性，并且似乎与 过敏部位2 因此，与该位点结合的因子是 候选人介导LCR和 珠蛋白启动子 此外，已知转录因子 调节其他转录因子的表达， 相互关系表明了一种复杂的相互作用层次结构， 调节特定组织中的特定基因产物， 在早期发展中发挥作用。 因此， 研究转录因子之间的相互关系将是重要的 了解这些基因在成人组织中的表达， 在早期发育过程中特定细胞的分化。 他们有 因此，也专注于EKLF红细胞特异性的调节， 转录因子基因 我们研究的具体目标如下： 1)一个新的5'端顺式元件的鉴定和表征 人B珠蛋白基因的侧翼序列。 我们将描述这一点 通过足迹法和寡核苷酸竞争研究， 结合该元件的因子将被分离和克隆， 酵母单杂交系统或常规方法。 2)调控 EKLF基因 转录因子基因的表达是高水平的 涉及红细胞和非红细胞的规范和既往研究 转录因子揭示了有趣的相互关系。 到 理解这个层次结构，我们计划定义cis元素， 负责组织特异性表达的反式因子 EKLF基因 总之，这些研究将提供新的见解， 基因调控机制以及造血生物学 系统.

DESCRIPTION: (Adapted from Abstract) The long term goal of the research is to understand the tissue and developmental-specific regulation of genes expressed in erythroid cells. The Investigators have concentrated on the regulation of genes in the b globin locus as a model of erythroid-specific gene expression. The regulation of these genes depends on transcription factors which are limited to erythroid cells or cells of closely related lineages, and on an organized chromatin structure dictated by the formation of hypersensitive sites within a region known as the LCR or locus control region. The investigations have led to the identification of a new cis element involved in the expression of the human b globin gene. This element confers a strong enhancer activity and appears to function in conjunction with hypersensitive site 2. Thus, the factor binding to this site is a candidate to mediate this critical interaction between the LCR and the globin promoter. In addition, it is known that transcription factors regulate the expression of other transcription factors and these interrelationships suggest a complex hierarchy of interaction that not only regulates specific gene products in a particular tissue, but also regulate each other to function in early development. It is thus likely that the study of the interrelationship among transcription factors will be important for understanding both the expression of these genes in adult tissue, and the differentiation of specific cells during early development. They have therefore also focused on the regulation of the EKLF erythroid-specific transcription factor gene. The specific aims of our studies are as follows: 1) Identification and characterization of a new cis element in the distal 5' flanking sequence of the human b globin gene. We will characterize this site through footprinting and oligonucleotide competion studies and the factor that binds the element will be isolated and cloned with the use of the yeast one-hybrid system or conventional procedures. 2) Regulation of the EKLF gene. The expression of transcription factor genes is highly regulated and previous studies involving both erythroid and non-erythroid transcription factors are revealing interesting interrelationships. To understand this hierarchy, we plan to define the cis elements and transacting factors responsible for the tissue-specific expression of the EKLF gene. Together, these studies will provide new insights into mechanisms of gene regulation as well as the biology of hematopoietic systems.