Dynamics of nucleosome positioning and the role of chromatin in myogenesis

核小体定位动力学和染色质在肌生成中的作用

• 批准号: 8253686
• 负责人: Dustin Edward Schones
• 金额: $ 26.89万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-06 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253686
• 关键词: Aging; Animal Model; Attention; Base Pairing; Binding; Cell Differentiation process; Cell Line; Cell Lineage; Cell Nucleus; Cells; Chromatin; Chromatin Remodeling Factor; Chromatin Structure; Cities; Critiques; DNA; DNA Sequence; DNA-Binding Proteins; Data; Development; Developmental Process; Distal; Drosophila genus; Drosophila melanogaster; Enhancers; Enzymes; Event; Gene Expression; Gene Expression Regulation; Genes; Genome; Goals; Grant; Hematopoietic; Hematopoietic System; Histones; Human; Human Genome; K562 Cells; Lead; Light; Maps; Mediator of activation protein; Modeling; Modification; Muscle Cells; Nucleic Acid Regulatory Sequences; Nucleosomes; Organism; Positioning Attribute; Post-Translational Protein Processing; Process; Proteins; Published Comment; RNA Sequences; Reading; Recruitment Activity; Regulation; Regulatory Element; Research; Role; Running; Stem cells; Structure; System; Technology; Time; Transcript; Transcription Coactivator; Transcriptional Regulation; Welts; Work; aged; cell fate specification; chromatin remodeling; clinically relevant; clinically significant; fly; genome-wide; histone modification; improved; insight; interest; knock-down; mammalian genome; multipotent cell; myogenesis; programs; promoter; research study; response; transcription factor

The DNA of eukaryotic organisms is pacl<aged into the nucleus by wrapping around histone proteins in a structure l<nown as chromatin. This pacl<aging can influence gene regulation with condensed chromatin regions containing genes and their associated regulatory elements that are inaccessible to transcriptional activators. The modulation of chromatin structure is therefore one of the key mediators of transcriptional regulation. The most basic unit of chromatin is the nucleosome, which consists of approximately 146 base pairs of DNA wrapped around an octamer of histone proteins. The precise positioning of nucleosomes in functional regulatory regions of the genome can directly influence the transcriptional regulation of nearby genes. ATP-dependent chromatin remodeling enzymes, post-translational modifications to histones and the DNA sequence itself have all been implicated in regulating the positioning of nucleosomes at specific regions of the genome. We propose to investigate the roles of each of these mechanisms in regulating the positioning of nucleosomes in the Drosophila melanogaster and human genomes and furthermore to begin to elucidate the relationship between chromatin and transcription factors in gene regulation. We will first investigate the basic questions of how chromatin remodeling enzymes are recruited to their targets and how ATP-dependent chromatin remodeling, histone modifications and DNA sequence interact to regulate nucleosome positioning by using cultured Drosophila cells. The insights obtained from these experiments in Drosophila cells will then be applied to analogous experiments in human hematopoietic cells, a system for which the network of transcription factors involved in lineage specification has been extensively studied. By integrating data on nucleosome positioning and chromatin remodeling with the already established transcription factor programs in these cells, I will be able to study the interactions between chromatin and transcription factors in regulating the transcriptional programs of cells during development. These studies will lead to a greater understanding of the mechanisms responsible for the organization of nucleosomes across the genome and further elucidate the role of chromatin in the regulation of transcription.

真核生物的DNA是通过缠绕进入细胞核的