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Defining the molecular and cellular mechanism of epigenetic transcriptional memory

定义表观遗传转录记忆的分子和细胞机制

基本信息

批准号：
9310277
负责人：
Jason Hays Brickner
金额：
$ 29.84万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310277
关键词：
Affect Affinity Aging Alpha Cell Binding Binding Proteins Biochemical Biological Models Cell division Cells Chromatin Structure Chromatin Structure Alteration Complex DNA Distant Elements Environment Epigenetic Process Exhibits FASTK Gene Fibrinogen Foundations Future Gene Expression Generations Genes Genetic Screening Genetic Transcription Goals Guanine Nucleotide Exchange Factors Hela Cells Heritability Histone Deacetylation Histone H3 Histones Homologous Gene Human Inherited Interferon Type II Interferons Label Life Style Lysine Mediating Memory Mitotic Modeling Molecular Mutation Nuclear Pore Nuclear Pore Complex Organism Physiological Physiology Pore Proteins Proteins RNA Polymerase II Recruitment Activity Repression Role Signal Transduction Stimulus Stress System Testing Time Trans-Activators Transcriptional Regulation Variant Work Yeast Model System Yeasts base experience experimental study gene interaction genome-wide mutant novel promoter protein folding public health relevance response

项目摘要

DESCRIPTION (provided by applicant): Understanding the molecular basis of epigenetic mechanisms that control the transcriptional response of cells to environmental signals is essential to understand how environment, aging and lifestyle impact physiology. My lab has discovered an evolutionarily conserved mechanism of epigenetically inherited transcriptional memory that involves the interaction of genes with nuclear pore proteins (8-10). Using both the INO1 gene from yeast and interferon γ-inducible genes in HeLa cells as models for transcriptional memory, we find that previously expressed genes interact with nuclear pore proteins for 4- 7 generations and this leads to an altered chromatin structure in the promoters of these genes. This allows RNA polymerase II to bind to these promoters, poising them for re-activation. We have now find that the scope of genes regulated by transcriptional memory includes dozens of stress-induced genes in yeast that utilize the same system. Therefore, transcriptional memory is a universal, ancient and conserved mechanism by which cells can integrate previous experience to affect future physiology. The goals of this work are to determine the molecular mechanisms that control establishment and inheritance of transcriptional memory in yeast and human cells.

描述（由申请人提供）：了解控制细胞对环境信号的转录反应的表观遗传机制的分子基础对于了解环境、衰老和生活方式如何影响生理学至关重要。我的实验室已经发现了表观遗传遗传转录记忆的进化保守机制，涉及基因与核孔蛋白的相互作用（8-10）。利用来自酵母的INO 1基因和HeLa细胞中的干扰素γ诱导基因作为转录记忆的模型，我们发现先前表达的基因与核孔蛋白相互作用4- 7代，这导致这些基因的启动子中的染色质结构改变。这使得RNA聚合酶II与这些启动子结合，使它们重新激活。我们现在发现，转录记忆调控的基因范围包括酵母中利用相同系统的数十个应激诱导基因。因此，转录记忆是一种普遍的、古老的和保守的机制，细胞可以通过它整合以前的经验来影响未来的生理。这项工作的目标是确定控制酵母和人类细胞中转录记忆建立和遗传的分子机制。