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Identification and characterization of novel epigenetic marks of non-histone prot

非组蛋白蛋白质的新型表观遗传标记的鉴定和表征

基本信息

批准号：
7690566
负责人：
Xiaodong Cheng
金额：
$ 23.92万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7690566
关键词：
Affect Affinity Amino Acids Antibodies Apoptosis Biological Biological Assay Biological Markers Biological Process CDC7 gene Cell Cycle Cell Cycle Progression Cell Extracts Cell Nucleus Cell division Cell physiology Cells Chemicals Chromatin Chromatin Structure Alteration Complex DNA DNA Damage DNA Packaging DNA Repair DNA biosynthesis Data Defect Dependence Development Disruption Dissection Epigenetic Process Eukaryotic Cell Evaluation Event Foundations Genetic Transcription Genome Stability Genomics Goals Growth Higher Order Chromatin Structure Histone H3 Histones Homologous Gene Human Human Genome In Vitro Link Localized Malignant Neoplasms Mammalian Cell Maps Mass Spectrum Analysis Meiosis Mitosis Modification Mutate Mutation Normal Cell Numbers Organism Output Pharmaceutical Preparations Phase Phosphorylation Phosphotransferases Play Ploidies Post-Translational Protein Processing Process Proliferating Protamine Kinase Protein Subunits Proteins Purpose RNA Interference Regulation Relative (related person)Replication Licensing Replication Origin Research Research Project Grants Role Saccharomyces cerevisiae Saccharomycetales Serine/Threonine Phosphorylation Site Testing Therapeutic Threonine Western Blotting Yeasts abstracting base cancer cell cancer therapy cell type chromatin immunoprecipitation chromatin remodeling genetic regulatory protein in vivo mutant novel research study temperature sensitive mutant

项目摘要

Abstract DNA in the nucleus of eukaryotic cells is packaged into the higher-order chromatin structure by histone proteins. Thus, DNA templated cellular processes require alteration of chromatin structure to dynamically facilitate access to packaged DNA. In general, this is accomplished by ATP-dependent chromatin remodeling, histone exchange or chemical modification of histone proteins. Phosphorylation of serine/threonine residues in particular has been shown to function in a number of cellular processes, including transcription, mitosis, apoptosis, and sporulation. We have isolated a novel histone kinase complex in yeast containing conserved S-phase regulatory proteins. This complex is capable of phosphorylating free histones, but targets histone H3 in the context of the intact histone octamer. Our preliminary data indicate that phosphorylation maps to a previously undescribed site of histone modification that may play a critical role in histone-DNA interactions and is likely of great significance to the process of DNA replication. The goals of this proposal are to purify and fully characterize the components of the multi-protein histone kinase activity, to characterize the function of this novel epigenetic mark in vivo and verify its dependence on the kinase complex in question. We also propose to map this modification on 1% of the human genome to assess its stability, localization and its suitability as a new epigenetic marker of replicating and proliferating cell types. Given our hypothesis that this modification functions in licensing of replication, we will also compare its relative abundance across the cell cycle and its requirement for cell cycle progression. As uncontrolled cell division and DNA replication is associated with the proliferation of cancer cells we anticipate that this epigenetic mark will provide a biomarker of diseased states and will offer a novel target for cancer therapeutics.

摘要