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Histone chaperone networks for new and evicted histones

新组蛋白和被驱逐组蛋白的组蛋白伴侣网络

基本信息

批准号：
10649735
负责人：
Daniel Richard Foltz
金额：
$ 33.02万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10649735
关键词：
Acetylation Binding Biology Cells Chromatin Chromatin Modeling Coupled Coupling DNA DNA Adduction DNA Adducts DNA biosynthesis DNA replication fork Data Dedications Deposition Disease Drops Elements Enzymes Gene Expression Genetic Transcription Genome Histone Acetylation Histone H3 Histone H4 Histones Knowledge Mentored Clinical Scientist Development Program Metabolic Control Metabolic Pathway Metabolism Methylation Modification Molecular Molecular Chaperones Nuclear Nucleosomes Nucleotide Biosynthesis Nucleotides Outcome Pathway interactions Population Post-Translational Protein Processing Process Proliferating Protein Isoforms Protein Subunits Proteins Regulation Role Slide Somatic Cell Source Specificity Structure Time Transferase Variant Work histone acetyltransferase histone methylation histone modification novel nucleotide metabolism prevent replication stress

项目摘要

Project Summary Nuclear DNA is packaged into nucleosomes by histone proteins to create chromatin. The assembly of chromatin is not a passive process but requires the activity of a network of histone-chaperone proteins that facilitate histone stability, prevent aggregation, organize histone transport and facilitate their deposition. Histone chaperones must deal with new histones, and also with pre-existing histones that are evicted from chromatin. DNA replication, DNA transcription and access to other control elements in the genome require nucleosomes be either moved out of the way (slid) or removed, resulting in the eviction of pre-existing histones. Specific chaperones contribute to the selective timing and placement of histone H3 variant deposition. However, many histone chaperones are agnostic about the variant or modification status of the histones they bind. Very little information exists as to how the chaperone pathways for new and pre-existing histone differ. NASP has long been appreciated as a key histone chaperone for histone H3 and histone H4, that functions irrespective of histone variant or posttranslational modification. NASP also binds the histone acetyltransferase enzyme HAT1 which contribute to the acetylation of new H4 histones at K12. Aim1 of this application will define novel interactions of NASP during DNA synthesis that contribute to new histone supply. Our work will also take an unbiased approach to ordering the process of histone-chaperone interaction during new histone deposition and histone eviction. A novel chaperone pathway for pre-existing nucleosomes that have been evicted from chromatin will be defined in aim 2 of the proposal. Finally, Aim 3 will define a novel mechanism for crosstalk between histone supply and nucleotide metabolism. Our work proposed in this application will define, for the first time, differential processes that regulate fate of new and pre-existing histones and provide a new paradigm for coordinated metabolic control.

项目总结