TRANSCRIPTIONAL INDUCTION BY THE HUMAN HMG 14 PROTEIN

许多生物过程，包括细胞生长的调节， 分化和发育是由固定的基因模式驱动的 表情。为了理解这些正常的细胞和 生物体过程的进展，以及它们如何在不同的 疾病状态，最重要的是理解基本的如何 在哺乳动物细胞中，转录可以被调节。所有细胞基因 是在染色质的背景下受到调节的，而且长期以来 认识到染色质在决定 基因的激活状态。 已知浓缩染色质既能抑制起始，又能抑制 RNA聚合酶的转录延伸。基因诱导 因此，表达通常需要将染色质重塑为 更具可扩展性的配置，以便既可以访问 活性染色质状态下的特异性DNA结合 高效地表达一个基因。最近，特定的蛋白质或复合体 已发现具有改变染色质能力的蛋白质 结构。特别是，我们和其他人已经表明， 保守的HMG-14/-17家族蛋白都可以改变更高的顺序 染色质结构与RNA聚合酶II促进转录 在拟议的研究中，我们将研究分子 通过染色质改变诱导转录的机制 HMG-14。特别是，我们将确定转录是否 HMG-14Alers组蛋白H1与染色质相互作用的激活区 以及转录活性HMG-14的结合是否特异性 与DNA结合的转录因子相互作用。这些研究应该 为理解一种潜在的新机制奠定基础 通过重新配置结构来介导转录诱导 在特定基因上的染色质。

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.