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Structural Mechanisms Controlling Cell-Cycle Gene Expression

控制细胞周期基因表达的结构机制

基本信息

批准号：
9892880
负责人：
Seth Michael Rubin
金额：
$ 32.82万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892880
关键词：
Architecture Binding Biochemical Biological Assay C-terminal Cell Cycle Cell Cycle Regulation Cell Proliferation Cell division Chromatin Chromatin Structure Complex Crystallization Cyclin-Dependent Kinases DNA DNA Binding DNA Binding Domain Data Defect Electron Microscopy Elements Gene Activation Gene Expression Gene Expression Regulation Genes Genetic Transcription Health Histone Code Histone H3 Histones Lead Link Malignant Neoplasms Mediating Mitosis Mitotic Modeling Molecular Neoplasm Metastasis Normal Cell Nucleosomes Phosphorylation Positioning Attribute Process Promoter Regions Proteins Publishing Repression Research Project Grants Research Project Summaries Shapes Structure System Testing Time Transcription Initiation Site Work cancer cell cdc Genes cell growth gene repression insight neoplastic cell novel outcome forecast promoter protein complex reconstitution recruit success transcription factor tumorigenesis

项目摘要

Project summary This research project aims to determine how the DREAM and Myb-MuvB (MMB) protein complexes regulate transcription to control cell proliferation. The conserved MuvB protein complex either represses or activates cell-cycle genes by timely association with specific DNA-binding transcription factors including E2F4-p130 (DREAM) and Myb (MMB). However, the biochemical function of the five protein MuvB complex is unknown. We propose and will test novel hypotheses for how MuvB associates with chromatin, how DREAM inhibits transcription by stabilizing chromatin structure, and how Myb activates gene expression through its association with MuvB. These studies will provide fundamental new insights regarding how the cell cycle is controlled and will uncover a novel mechanism for how transcription factors directly modulate gene expression through nucleosome positioning.

项目总结该研究项目旨在确定Dream和Myb-MuvB(MMB)蛋白是如何复合体调节转录以控制细胞增殖。保守的MuvB 蛋白质复合体通过与细胞周期基因的适时结合抑制或激活细胞周期基因特异性DNA结合转录因子包括E2F4-p130(DREAM)和Myb (MMB)。然而，五种蛋白MuvB复合体的生化功能尚不清楚。我们提出并将测试MuvB如何与染色质相关联的新假设， DREAM如何通过稳定染色质结构抑制转录，以及Myb如何通过与MuvB的结合激活基因表达。这些研究将提供关于细胞周期如何控制的基本新见解，并将揭示转录因子直接调控基因表达的新机制通过核小体定位。