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Chromatin Remodeling and Transcription Repression

染色质重塑和转录抑制

基本信息

批准号：
7620221
负责人：
Blaine Bartholomew
金额：
$ 7.08万
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 2008-12-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7620221
关键词：
ATP phosphohydrolase Acetylation Affect Binding Catalytic Domain Chromatin Chromatin Fiber Chromatin Remodeling Factor Chromatin Structure Class Complex DNA DNA Binding DNA Footprint DNA Repair DNA biosynthesis Eukaryota Eukaryotic Cell Family Genes Genetic Transcription Goals Higher Order Chromatin Structure Histones ISWI Maps Mass Spectrum Analysis Mediating Meiosis Methods Methylation Modeling Modification Molecular Conformation Monitor Nucleosomes Positioning Attribute Printing Process Property Protein Footprinting Proteins Proteolysis Reaction Recruitment Activity Repression Repressor Proteins Resolution Saccharomyces cerevisiae Site Site-Directed Mutagenesis Structure Surface System Techniques Transcriptional Regulation analog chromatin remodeling deletion analysis foot gene repression repaired time interval transcription termination

项目摘要

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 ISWl and ISW2. The Iswlp protein is assembled into two distinct complexes referred to as ISWla and ISWlb; 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. ISWla/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 ISWl bind to nucleosomes, what are the structural intermediates involved in remodeling, and how do these changes affect the higher ordered structure of chromatin.

依赖于ATP的染色质重塑参与转录、DNA复制、重组和DNA修复。通常，这种染色质重塑与制造DNA有关更容易与其他DNA结合因子结合，从而促进其与特定靶点的结合。一一类依赖于ATP的染色质重塑复合体，被称为模拟开关(ISWI)家族，具有整体调节染色质结构，形成抑制性染色质结构，以及参与转录抑制的可能性。在酿酒酵母中，有两个类似ISWL的基因，即ISW1和ISW2。Iswlp蛋白组装成两个不同的复合体，称为 ISW1a和ISW1b，而ISW2只有一个复合体。ISW2已被证明是抑制减数分裂基因，并被Ume6抑制蛋白招募。ISWla/b也被最近发现与转录终止有关。目前还不清楚这些复合体是如何重塑的核小体和染色质的净结构变化。我们实验室的结果和那些 Peter Becker已经证明，ISWI的重塑不会改变正则核小体结构和然而，也很明显，这些确实促进了更紧密的染色质纤维结构的形成。我们的建议确定ISW2和ISWL如何与核小体结合，结构中间体是什么参与重塑，以及这些变化如何影响染色质的高级有序结构。