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Role of MRG15 in Chromatin Changes During Cell Senescence and In Vivo Aging

MRG15 在细胞衰老和体内衰老过程中染色质变化中的作用

基本信息

批准号：
7666128
负责人：
OLIVIA M. PEREIRA-SMITH
金额：
$ 29.33万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7666128
关键词：
Accounting Acetylation Adenoviruses Affect Age Aging Aging-Related Process Animals Antibodies BRCA1 gene Binding Proteins Biological Assay Blood Brain Bromodeoxyuridine Cell Aging Cell Count Cell Culture System Cell Cycle Proteins Cell Extracts Cell Proliferation Cell physiology Cells Cervix carcinoma Chromatin Chromatin Remodeling Factor Chromatin Structure Comet Assay Complex Cultured Cells Cyclin A DNA DNA Damage DNA Repair DNA Structure DNA Synthesis Induction DNA biosynthesis DNA methyltransferase inhibition Data Development Diploidy Dosage Compensation (Genetics)Drosophila genus Embryo Essential Genes Exclusion Exons Fibroblasts Gene Deletion Gene Expression Gene Expression Regulation Gene Family Gene Targeting Genes Genetic Transcription Goals Growth Factor Hela Cells Hepatocyte High Pressure Liquid Chromatography Histone Deacetylase Histone Deacetylation Histones Human In Vitro Individual Infection Kidney Knockout Mice Knowledge Laboratories Lead Lethal Genes Leucine Zippers Liver Lung Microtus Modeling Molecular Sieve Chromatography Molecular Weight Mus N-terminal Nuclear Localization Signal Nuclear Protein Nuclear Proteins Nucleoproteins Null Lymphocytes Paraffin Embedding Partial Hepatectomy Peptide Signal Sequences Phenotype Play Prevalence Process Promoter Regions Proteins RNA Regulation Relaxation Reporter Reporting Role Site Stress Structure System TRRAP gene Testing Testis Time Tissues Transcriptional Activation Transcriptional Regulation Transfection Western Blotting X Chromosome Yeasts base biological systems bladder Carcinoma cell age cell type chromatin immunoprecipitation chromatin remodeling embryonic stem cell fly in vivo inhibitor/antagonist interest irradiation male member middle age mouse model oncoprotein p21 promoter protein complex protein function protein protein interaction repaired research study response senescence

项目摘要

The overall goal of this project is to elucidate the role of chromatin remodeling during in vitro and in vivo aging. It is becoming increasingly clear that chromatin remodeling is essential for gene expression regulation and organization of DMA structure to allow for repair of DNA damage. MRG15, which is clearly involved in various aspects of chromatin remodeling, therefore serves as an excellent model gene for the study of the importance of changes in chromatin structure on gene expression and DNA repair during the aging process. MRG15 was cloned in our laboratory in the course of our studies of cellular aging, as one of three members of the MORF/MRG family of genes that is expressed. It shares common motifs with MORF4 and MRGX that include a leucine zipper, HLH region and nuclear localization signal sequences, which uggest these proteins will be involved in transcriptional regulation via protein-protein interactions. However, n the N-terminal domain of only MRG15 is a chromodomain motif, which is highly similar to that in the ms!3 (male specific lethal) gene of Drosophila, which is required for activation of transcription of the entire X chromosome in male flies, the dosage compensation mechanism. This chromodomain has now been mplicated as essential for recruitment of MRG15 as a component of the Tip60 histone acetyltranserase complex to sites where chromatin remodeling must occur. This includes regions where transcription activation is to occur and also sites of damaged DNA. Chromatin remodeling precedes the recruitment of nuclear protein complexes involved in transcription or DNA repair. MRG15 is a highly conserved protein and s present in yeast to human. The protein components of the complexes it associates with are also highly conserved. It is therefore not surprising that deletion of this gene in mice or Drosophila results in embryonic ethality. In this proposal we plan to determine the role of MRG15 in cell proliferation control and DNA damage repair using both cell culture systems, young and old C57BI6 mice and the MRG15 heterozygous mouse model. We will characterize the various protein complexes involved, their changes during in vitro and n vivo aging and the impact of these changes on function of cells and tissues. The results will not only tie ogether in vitro and in vivo information, but also increase our knowledge of how and when nuclear protein omplexes act and better define the role of chromatin remodeling during aging.

本项目的总体目标是阐明染色质重塑在体外和体内的作用