Dynamic Nucleosome Signatures in Epigenetic Memory and Cancer Development

表观遗传记忆和癌症发展中的动态核小体特征

基本信息

批准号：
8549140
负责人：
William Lawrence Kath
金额：
$ 23.9万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8549140
关键词：
Affect Alleles Animal Model B-Cell Neoplasm Back Behavior Biological Models Breast Carcinoma Cell Culture Techniques Cell Line Cell model Cells ChIP-seq Characteristics Chromosomal Rearrangement Code Computer Simulation Conditioned Culture Media DNA Data Data Set Deoxycytidine Development Disseminated Malignant Neoplasm Embryo Epigenetic Process Exhibits Fibroblasts Gene Chips Gene Expression Gene Silencing Genes Genetic Goals Histones Human Infection Knock-out MCF7 cell MEL Gene MLH1 gene Maintenance Malignant Epithelial Cell Malignant Neoplasms Maps Mature B-Lymphocyte Measurement Memory Methods Methylation Modeling Modification Molecular Molecular Profiling Multiple Myeloma Myeloproliferative disease Nature Nodal Nucleosomes Nude Mice Oncogenes Phosphotransferases Point Mutation Positioning Attribute Process Proteins Protocols documentation Recombinants Regulation Resolution Simian virus 40 Stem cells Stochastic Processes System T47D Telomerase Tetanus Helper Peptide Theoretical model Transferase Translations Viral Tumor Antigens Work Yeasts base cancer cell cell type demethylation embryonic stem cell genetic element genome-wide histone modification homologous recombination human embryonic stem cell immortalized cell induced pluripotent stem cell inhibitor/antagonist interest kidney cell mutant network models overexpression pluripotency predictive modeling programs promoter research study small hairpin RNA stem theories tumor tumorigenic

项目摘要

Increasing evidence indicates that cancer results not only from changes in genetic information; in the form of point mutations, chromosomal rearrangements, gene segment amplification and deletion, but also from changes in epigenetic information. Recent theoretical analyses of epigenetic regulation in a model organism (yeast) show that ideas from the dynamical systems field may explain the stability of epigenetic states and the dynamics of spontaneous changes between them. This project will experimentally define the epigenetic changes resulting from the action of (1) a mutant kinase JAK2V617F, a causative factor in myeloproliferative disease; (2) a defined set of oncogenes that transform normal human cells to cancer cells (T antigen, ras, shRNA PP2a, telomerase); and (3) the changes in state of the MLH1 promoter that accompany gene silencing associated with promoter methylation, and reactivation that is induced by 5-aza-2'-deoxycytidine and is associated with DNA demethylation. We will use this information to develop quantitative predictive models of epigenetic inheritance and switching in these systems, based on a dynamical systems framework.