Chromatin Remodeling and Transcription Repression

染色质重塑和转录抑制

• 批准号: 6766313
• 负责人: Blaine Bartholomew
• 金额: $ 22.17万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766313
• 关键词: DNA binding protein; DNA footprinting; Saccharomyces cerevisiae; acetylation; chromatin; fungal genetics; gene induction /repression; histones; mass spectrometry; methylation; nucleosomes; site directed mutagenesis

DESCRIPTION (provided by applicant): ATP-dependent chromatin remodeling is involved in the regulation of transcription, DNA replication, recombination, and DNA repair. Often this kind of chromatin remodeling is associated with making the DNA more accessible to other DNA-binding factors thereby promoting their binding to specific target sites. One class of ATP-dependent chromatin remodeling complexes, referred to as imitation switch (ISWI) family, has the general properties of globally regulating chromatin structure, forming repressive chromatin structures, and of being involved in transcription repression. In Saccharomyces cerevisiae there are two ISWl like genes, namely ISW1 and ISW2. The Isw1p protein is assembled into two distinct complexes referred to as ISW1a and ISW1b; whereas only one complex of ISW2 is found. ISW2 has been shown to be required for repression of meiotic genes and to be recruited by the Ume6 repressor protein. ISW1a/b have also been recently shown to be involved in transcription termination. It is not clear yet how these complexes remodel nucleosomes and what the net structural changes caused in chromatin. Results from our lab and those of Peter Becker have shown that ISWI remodeling does not change the canonical nucleosome structure and yet it is also clear that these do promote the formation of a more condensed chromatin fiber structure. Our proposal is to determine how ISW2 and ISW1 bind to nucleosomes, what are the structural intermediates involved in remodeling, and how do these changes affect the higher ordered structure of chromatin.

描述（由申请人提供）：ATP依赖性染色质重塑与转录，DNA复制，重组和DNA修复的调节有关。通常，这种染色质重塑与使DNA更容易与其他DNA结合因子访问，从而促进其与特定靶位点的结合。一类依赖ATP的染色质重塑复合物（称为模仿开关（ISWI）家族）具有全球调节染色质结构，形成抑制性染色质结构的一般特性，并参与转录抑制。在酿酒酵母中，有两个ISWL，例如基因，即ISW1和ISW2。 ISW1P蛋白被组装成两个不同的复合物，称为ISW1A和ISW1B。而仅发现一个ISW2的一个复合物。已经证明ISW2是对减数分裂基因抑制所必需的，并由UME6抑制剂蛋白募集。 ISW1A/B最近也已显示与转录终止有关。尚不清楚这些复合物如何重塑核小组以及染色质中净结构变化是什么。我们实验室和彼得·贝克尔（Peter Becker）的结果表明，ISWI重塑不会改变规范的核小体结构，但很明显，这些结构确实促进了更凝结的染色质纤维结构的形成。我们的建议是确定ISW2和ISW1如何与核小体结合，与重塑有关的结构中间体是什么，以及这些变化如何影响染色质的较高有序结构。