Transcriptional Repression by Histone Amino Termini in Yeast

该项目的长期目标是了解组蛋白氨基末端，特别是组蛋白H3的氨基末端，在体内对转录抑制的贡献程度，并确定它们这样做的机制。 真核DNA被包装成染色质，而染色质的基本单位核小体由大约146个碱基对的DNA包裹在组蛋白核心周围组成。 有些令人惊讶的是，组蛋白的非结构化氨基末端的修饰，这不是核小体的基本结构组成部分，已被证明是一种广泛使用的基因调控手段。 许多研究表明，组蛋白氨基末端的修饰参与了多种细胞过程的转录调控，包括细胞周期控制、激素反应和发育。 尽管取得了这些进展，但对组蛋白氨基末端影响转录调控的机制知之甚少。 主要研究者发现了两个例子，其中组蛋白H3氨基末端对酵母中的转录抑制至关重要。 在第一个实施例中，H3氨基末端防止在不存在诱导物的情况下由CHA 4激活剂在CHA 1启动子处激活。 在第二个例子中，INO 1基因在没有H3氨基末端的情况下被强烈去阻遏，尽管目前对机制知之甚少。 首席研究员还发现，使用微阵列技术，H3氨基末端对基因表达产生广泛的、全基因组的抑制作用。 这些发现作为确定H3氨基末端抑制的具体机制的基础。 此外，我们还将通过实验研究组蛋白H3和H4的氨基末端在组蛋白去乙酰化酶RPD 3介导的阻遏中的作用。DNA是生命的主控制器和信息库。 在非细菌细胞中，DNA与染色质中的组蛋白结合。 这些蛋白质帮助DNA适应细胞内部，并参与调节许多使用DNA的过程，包括将DNA转录成RNA-DNA中信息的“读出”。 首席研究员使用面包酵母进行的研究旨在了解组蛋白的特定部分如何阻止特定基因在不应该被转录时被转录。 由于转录的基本机制和染色质组分在酵母和高等生物中非常相似，这些发现将为所有非细菌生物的转录调控提供新的线索。

The long term goals of this project are to understand the extent to which the histone amino termini, especially that of histone H3, contribute to transcriptional repression in vivo, and to determine the mechanisms by which they do so. Eukaryotic DNA is packaged into chromatin, and the fundamental unit of chromatin, the nucleosome, consists of about 146 base pairs of DNA wrapped around a core of histone proteins. Somewhat surprisingly, modification of the unstructured amino termini of the histones, which are not an essential structural component of the nucleosome, has turned out to be a widely used means of gene regulation. Numerous studies have implicated transcriptional regulation via modifications of the histone amino termini in diverse cellular processes, including cell cycle control, hormone response, and development. In spite of this progress, little is known of the mechanisms by which the histone amino termini influence transcriptional regulation. The principal investigator has discovered two examples in which the histone H3 amino terminus is critical for transcriptional repression in yeast. In the first example, the H3 amino terminus prevents activation by the CHA4 activator at the CHA1 promoter in the absence of inducer. In the second example, the INO1 gene is strongly derepressed in the absence of the H3 amino terminus, although little is known about the mechanism at present. The principal investigator has also found, using micorarray technology, that the H3 amino terminus exerts a broad, genome-wide repressive effect on gene expression. These findings serve as a basis to determine specific mechanisms for repression by the H3 amino terminus. In addition, experiments will be done to examine the contribution of the amino termini of histones H3 and H4 as targets in repression mediated by the histone deacetylase RPD3.DNA is the master controller and information reservoir for all of life. In non-bacterial cells, DNA is bound to histone proteins in chromatin. These proteins help the DNA fit inside the cell and participate in regulation of many processes that use DNA, including the transcription of DNA into RNA-the "readout" of the information in DNA. Studies by the principal investigator, using baker's yeast, are aimed at understanding how specific parts of the histone proteins prevent particular genes from being transcribed when they are not supposed to be. Because the basic mechanisms of transcription and components of chromatin are very similar in yeast and higher organisms, these findings will shed new light on transcriptional regulation in all non-bacterial organisms.