Chromatin Remodeling and Transcription Repression

染色质重塑和转录抑制

基本信息

批准号：
7025055
负责人：
Blaine Bartholomew
金额：
$ 21.64万
依托单位：
SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
依托单位国家：
美国
项目类别：
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/7025055
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

项目摘要

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依赖性染色质重塑参与转录、DNA复制、重组和DNA修复的调节。通常，这种染色质重塑与使 DNA 更容易接触其他 DNA 结合因子有关，从而促进它们与特定靶位点的结合。一类ATP依赖性染色质重塑复合物，称为模仿开关（ISWI）家族，具有全局调节染色质结构、形成抑制性染色质结构以及参与转录抑制的一般特性。在酿酒酵母中，存在两个ISW1样基因，即ISW1和ISW2。 Isw1p 蛋白被组装成两个不同的复合物，称为 ISW1a 和 ISW1b；而仅发现了 ISW2 的一种复合物。 ISW2 已被证明是减数分裂基因抑制所必需的，并被 Ume6 抑制蛋白招募。 ISW1a/b 最近也被证明参与转录终止。目前尚不清楚这些复合物如何重塑核小体以及染色质的净结构变化引起什么。我们实验室和 Peter Becker 的结果表明，ISWI 重塑不会改变典型的核小体结构，但也很明显，这些确实促进了更浓缩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，参与重塑的结构中间体是什么，以及这些变化如何影响染色质的高级有序结构。