Role of the histone chaperone Rtt106 in transcription elongation, chromatin dynamics and regulation of cryptic site transcription

组蛋白伴侣 Rtt106 在转录延伸、染色质动力学和隐秘位点转录调控中的作用

• 批准号: 326942-2006
• 负责人: Nourani, Amine
• 金额: $ 3.1万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=337439
• 关键词: Role; histone; chaperone; Rtt106; transcription

Gene expression is a key mechanism involved in the control of cellular processes (growth, differentiation and death). A defect in the regulation of gene expression can have dramatic consequences such as failure in cell cycle control, leading to cancer. To understand how transcription works one must consider that eukaryotic DNA is packaged into a condensed structure called chromatin. In addition to a structural role, chromatin represses different step of transcription. We are interested by chromatin dynamics associated to the elongation of transcription. It seems that a defect in this step affects the cellular homeostasis and result in various diseases including myeloid leukemia, Cockayne syndrome and the familial cancer predisposition syndrome von Hippel-Lindau disease. It is not clear of how elongation contribute to these diseases. In order to gain more insights about these diseases, we are interested by chromatin dynamics associated to transcription elongation. To study transcription elongation, we decided to use a very powerful model organism that is the yeast Saccharomyces cerevisiae. Importantly, transcription mechanisms are well conserved throughout the evolution scale and major discoveries in this research field were made using this organism. We will combine genetic, biochemical and genomic approaches to understand how transcription elongation deals with chromatin structure. We will specifically study the protein machines that remodel and assemble chromatin during transcription. These studies will result in better understanding of elongation and may therefore lead to envision new therapies.

基因表达是参与控制细胞过程（生长、分化和死亡）的关键机制。基因表达调控的缺陷可能会产生严重的后果，如细胞周期控制失败，导致癌症。为了理解转录是如何工作的，我们必须考虑真核生物的DNA被包装成一种叫做染色质的浓缩结构。除了结构作用外，染色质还抑制转录的不同步骤。我们感兴趣的是与转录延长相关的染色质动力学。这一步骤的缺陷似乎会影响细胞的稳态，并导致各种疾病，包括骨髓性白血病，Cockayne综合征和家族性癌症易感综合征von Hippel-Lindau病。目前尚不清楚伸长如何导致这些疾病。为了更深入地了解这些疾病，我们对与转录延伸相关的染色质动力学感兴趣。为了研究转录延伸，我们决定使用一种非常强大的模式生物，即酿酒酵母。重要的是，转录机制在整个进化尺度上都很保守，并且使用这种生物体进行了该研究领域的重大发现。我们将结合联合收割机遗传学、生物化学和基因组学的方法来了解转录延伸如何处理染色质结构。我们将专门研究在转录过程中重塑和组装染色质的蛋白质机器。这些研究将导致更好地理解延长，因此可能导致设想新的治疗方法。