ROLE FOR TRANSCRIPTION FACTOR LSF IN MAMMALIAN CELLS

精确的基因表达程序控制着许多复杂的生物 过程，包括细胞的生长、分化和发育。一个 阐明了正常对照被颠覆的机制， 发生在各种肿瘤和某些新生儿的发育过程中 缺陷，因此需要对监管有一个基本的了解 基因表达。启动所需的转录机制 RNA聚合酶II启动子的转录过程相当复杂，包括 特定的DNA结合蛋白，它只控制转录 包含其识别序列的启动子。 SV40晚期启动子的表达在 SV40对细胞的裂解感染。细胞转录因子LSF， 它刺激主要的晚期SV40起始点的转录， 结合两个不同的启动子元件，以45和265个核苷酸为中心 这个迟来的起始点。这些研究的广泛目标是确定 LSF在SV40裂解过程中转录调控中的作用 周期和哺乳动物细胞内。将解决的具体目标 这个广泛的目标是：(1)克隆LSF的基因，并定义 蛋白质的DNA结合区和转录激活区； LSF在两次识别时蛋白质-DNA相互作用的详细研究 并确定DNA的弯曲和/或不同 LSF的构象在差异识别中起作用；(3) 确定SV40内两个LSF结合位点的功能 启动子；(4)确定LSF刺激的机制 转录；(5)研究LSF和LSF之间的潜在相互作用 结合在相邻或重叠序列上的转录因子，以及(6) 确定LSF活性是否受SV40感染的调节。 LSF(一种细胞蛋白)也可能在调节 细胞基因的表达。LSF专门结合邻近的序列 C-fos启动子中的血清反应元件。此外，还包括多个 细胞周期调节的人胸苷酸合成酶和 胸苷激酶启动子与LSF识别位点高度同源。 LSF的细胞功能将通过描述LSF结合来解决 细胞启动子内的位点，确定LSF是激活还是 抑制这些启动子的转录，决定LSF 活性由血清、确定的生长因子或在细胞内调节 周而复始。这些研究将有助于确定LSF是否调节基因表达 对特定的细胞外信号做出反应。

Precise programs of gene expression control many complex biological processes, including cell growth, differentiation, and development. An elucidating of the mechanisms by which the normal controls are subverted, as occurs in various neoplasms and during the development of some birth defects, will therefore require a basic understanding of the regulation of gene expression. The transcription machinery required for the initiation of transcription at RNA polymerase II promoters is quite complex, including specific DNA-binding proteins, which control transcription only at promoters containing their recognition sequences. Expression from the SV40 late promoter is exquisitely regulated during lytic infection of cells with SV40. The cellular transcription factor LSF, which stimulates transcription from the major late SV40 initiation site, binds two distinct promote elements centered at 45 and 265 bp upstream of this late initiation site. The broad goal of these studies is to define the role of LSF in regulation of transcription both during the SV40 lytic cycle and within the mammalian cell. The specific aims that will address this broad goal are: (1) to clone the gene for LSF, and define both the DNA-binding and transcriptional activation regions of the protein; (2) to study in detail the protein-DNA interactions of LSF at its two recognition sites, and to determine whether bending of DNA and/or different conformations of LSF play a role in the differential recognition; (3) to determine the function of the two LSF binding sites within the SV40 promoters; (4) to determine the mechanism by which LSF stimulates transcription; (5) to investigate potential interactions between LSF and transcription factors binding at adjacent or overlapping sequences, and (6) to determine whether LSF activity is regulated by SV40 infection. LSF (a cellular protein) is likely to also play a role in regulating expression of cellular genes. LSF specifically binds sequences adjacent to the serum response element in the c-fos promoter. In addition, multiple sequences within the cell cycle-regulated human thymidylate synthase and thymidine kinase promoters are highly homologous to LSF recognition sites. The cellular function of LSF will be addressed by delineating LSF binding sites within cellular promoters, determining whether LSF activates or represses transcription of these promoters, determining whether LSF activity is regulated by serum, defined growth factors, or during the cell cycle. These studies will help determine if LSF regulates gene expression in response to specific extracellular signals.