TRANSCRIPTIONAL INDUCTION BY THE HUMAN HMG 14 PROTEIN

许多生物过程，包括细胞生长的调节， 分化和发育是由基因的固定模式驱动的。 表情 为了了解这些正常的细胞和 生物过程的进展，以及它们如何在各种 疾病状态，最重要的是要了解如何的基础知识 在哺乳动物细胞中可以调节转录。 所有细胞基因 是在染色质环境中调节的， 认识到染色质在决定细胞的增殖中起着核心作用。 基因的激活状态。 已知凝聚的染色质抑制细胞分裂的起始和 RNA聚合酶延长转录。 诱导基因 因此，表达通常需要将染色质重塑为 更扩展的配置，以便它变得可以访问， 在活性染色质状态下特异性DNA结合， 有效地表达一个基因。 最近，特异性的蛋白质或复合物， 已经鉴定出能够改变染色质的蛋白质 结构 特别是，我们和其他人已经表明， 保守的HMG-14/-17蛋白家族都可以改变更高的顺序 染色质结构和促进RNA聚合酶II转录 和三. 在拟议的研究中，我们将研究分子 机制，通过染色质改变，转录诱导， HMG-14 特别是，我们将确定是否转录 HMG-14的活化区alers组蛋白H1-染色质相互作用 以及是否转录活性HMG-14特异性地 与DNA结合转录因子相互作用。 这些研究应 为理解一种潜在的新机制奠定基础 通过重组结构来介导转录诱导 在特定的基因上。

Many biological processes, including the regulation of cell growth, differentiation, and development are driven by fixed patterns of gene expression. In order to understand how these normal cellular and organismal processes progress, as well as how they go awry in various disease states, it is paramount to comprehend the basics of how transcription can be regulate in mammalian cells. All cellular genes are regulated within a chromatin context, and it has long been appreciated that chromatin plays a central role in determining the activation state of a gene. Condensed chromatin is known to inhibit both the initiation and elongation of transcription by RNA polymerase. Induction of gene expression therefore often requires remodeling of the chromatin to a more extended configuration, so that it becomes accessible both to specific DNA-binding in the active chromatin state in order to efficiently express a gene. Recently, specific proteins or complexes of proteins have been identified that have the capability to alter chromatin structure. In particular, we and others have shown that the highly conserved HMG-14/-17 family of proteins can both alter higher order chromatin structure and facilitate transcription by RNA polymerase II and III. In the proposed study, we will investigate the molecular mechanism, via chromatin alterations, of transcriptional induction by HMG-14. In particular, we will determine whether the transcriptional activation region of HMG-14 alers histone H1-chromatin interactions and whether the binding of transcriptionally active HMG-14 specifically interacts with DNA-binding transcription factors. These studies should lay the groundwork for understanding a potentially novel mechanism for mediating transcriptional induction by reconfiguring the structure of chromatin at specific genes.