REGULATION OF ERYTHROPOIETIN AND HEMOGLOBIN GENE EXPRESSION

这项建议的长远目标是， 在分子水平上理解， 血红蛋白的合成以及促红细胞生成素在其中的作用 调控 促红细胞生成素作用机制的一方面 红细胞分化的启动和控制 珠蛋白基因的转录。 转化的小鼠细胞 系，IW32和NN10，其组成型分泌促红细胞生成素， 是研究这一过程的好模型，因为它们也可以 被氯化血红素或丁酸盐诱导，转录α和β 珠蛋白基因座 对照细胞系（201），其不分泌 促红细胞生成素，转录α珠蛋白信息， 在暴露于氯高铁血红素或丁酸盐之后的β。 因此，问题是 差异基因表达的机制以及 反式作用的作用，抑制因子的调节， β珠蛋白基因 该模型可能与各种人类 其中球蛋白基因不表达或 表达，并应予以抑制，以允许表达一个 替代. IW32细胞有一个重排和扩增的 促红细胞生成素基因，并被用于研究结构 允许促红细胞生成素组成型表达的特征 基因

The long-term objective of this proposal is a more complete understanding, at the molecular level, of the regulation of hemoglobin synthesis and the role of erythropoietin in this regulation. One aspect of the mechanism of erythropoietin action on red cell differentiation is that of initiation and control of transcription of the globin genes. The transformed mouse cell lines, IW32 and NNlO, which secrete erythropoietin constitutively, are good models in which to study this process since they can also be induced, by hemin or butyrate, to transcribe the alpha and beta globin loci. A control cell line (201), which does not secrete erythropoietin, transcribes the alpha globin message but not the beta after exposure to hemin or butyrate. The problem thus is one of the mechanism of differential gene expression and the possible role of trans-acting, inhibitory factors in the regulation of the beta globin gene. This model may be related to various human disorders in which either a globin gene is not expressed or one is expressed and should be suppressed to permit the expression of an alternative. IW32 cells have a rearranged and amplified erythropoietin gene and are being used to study the structural features that permit constitutive expression of the erythropoietin gene.