STRUCTURE STUDIES OF TRANSCRIPTIONAL SILENCING

转录沉默的结构研究

• 批准号: 6361956
• 负责人: RUI-MING XU
• 金额: $ 29.06万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6361956
• 关键词: Archaea; DNA binding protein; DNA replication origin; Saccharomyces cerevisiae; X ray crystallography; amidohydrolases; bacterial proteins; chromatin; computer data analysis; computer simulation; crystallization; enzyme substrate complex; functional /structural genomics; fungal proteins; gene induction /repression; histones; intermolecular interaction; model design /development; molecular assembly /self assembly; molecular biology information system; molecular site; nicotinamide adenine dinucleotide; physical model; protein structure function; site directed mutagenesis; structural biology

Transcriptional silencing is an epigenetic mechanism for control of gene expression. Genes located in certain regions of the eukaryotic chromosomes are permanently repressed. This heritable transcriptionally silent state is caused by altered chromatin structure that can be propagated from one generation to the next. Gene silencing has been observed in organisms ranging from yeast to human. Examples of silencing include mating-type loci in fission and budding yeasts, position effect variegation in Drosophila, and X-chromosome inactivation in mammals. In Saccharomyces cerevisiae, several protein complexes are known to be critical for establishing and maintaining transcriptional silencing at several genomic loci. They include the Silent Information Regulator proteins, Sir1p, Sir2p, Sir3p and Sir4p, and several sequence-specific DNA binding proteins, the Origin Recognition Complex (ORC), Rap1p and Abf1p. The structural basis of transcriptional silencing is still poorly understood. We will study the structure and function of the SIR proteins and ORC using X-ray crystallography as our principal method. The result of this study may facilitate an understanding of epigenetic inheritance, DNA repair and aging.

转录沉默是控制基因表达的表观遗传机制。位于真核染色体某些地区的基因被永久抑制。这种可遗传的转录静音状态是由染色质结构改变引起的，可以从一代到下一代传播。在酵母到人类的生物中已经观察到基因沉默。沉默的例子包括裂变和萌芽酵母中的交配型基因座，果蝇中的位置效应变化以及哺乳动物中的X染色体灭活。在酿酒酵母中，已知几种蛋白质复合物对于在几个基因组基因局建立和维持转录沉默至关重要。它们包括无声信息调节蛋白，SIR1P，SIR2P，SIR3P和SIR4P，以及几种序列特异性DNA结合蛋白，原点识别复合物（ORC），RAP1P和ABF1P。转录沉默的结构基础仍然很少了解。我们将使用X射线晶体学作为我们的主要方法研究SIR蛋白质和兽人的结构和功能。这项研究的结果可能有助于了解表观遗传遗传，DNA修复和衰老。