UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC TRANSCRIPTIONAL SILENCING

了解表观遗传转录沉默的分子基础

• 批准号: 8360578
• 负责人: Yvonne Nsokika Fondufe-Mittendorf
• 金额: $ 18.38万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360578
• 关键词: Alpha Cell; Binding; Cells; Centers of Research Excellence; Chromatin; Complex; Data; Development; Epigenetic Process; Equilibrium; Event; Freezing; Funding; Gene Expression Regulation; Gene Silencing; Genes; Grant; Growth; Histones; Homeostasis; Malignant Neoplasms; Measures; Molecular; National Center for Research Resources; Partner in relationship; Pattern; Polymerase Chain Reaction; Principal Investigator; Regulator Genes; Relative (related person); Research; Research Infrastructure; Resources; Source; Structure; System; Testing; Time; Transcription Factor TFIIB; United States National Institutes of Health; Yeasts; base; chromatin immunoprecipitation; cost; gene repression; human disease; promoter; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Epigenetic silencing, the heritable repression of transcription within chromatin domains, is critical in eukaryotic gene regulation. Maintaining homeostasis requires a delicate balance of gene regulatory events involving transcription factors. Deregulation of silencing patterns ushers growth of aberrant cells, and development and proliferation of cancer. However, the molecular mechanism of epigenetic silencing remains unknown. My previous data indicate that silencing is initiated downstream of activator binding but upstream of TFIIB recruitment and preinitiation-complex assembly suggesting silencing acts through posttranslationally modifying histones, to govern TFIIB recruitment to promoters. This project aims to identify transcription factors and molecular mechanisms responsible for transcriptional silencing. We will determine the essential regulators of silenced genes by backtracking from TFIIB binding to activator binding and quantify the relative occupancy of these crucial regulators at silenced versus active genes. Utilizing the silenced mating system in yeast to examine the mechanism of silencing in a natural context, the extent of occupancy of key regulatory factors at the silenced/active mating loci in "a" and "alpha" cells, will be measured by chromatin immunoprecipitation and real-time polymerase chain reaction. We will test the hypothesis that these key regulators control silencing through ongoing, reversible, dynamic competition rather than through frozen, inert structure.

这个子项目是利用这些资源的众多研究子项目之一