Uncovering a new role of nucleosomes in gene regulation

揭示核小体在基因调控中的新作用

• 批准号: 9922463
• 负责人: Feng Cui
• 金额: $ 6.93万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922463
• 关键词: Address; Affect; Algorithms; Animal Model; Apoptosis; Binding; Binding Sites; Biological; Cell Cycle Arrest; Cessation of life; Chromatin; Communities; DNA; DNA Binding; DNA-Binding Proteins; Data; Decision Making; Electrophoretic Mobility Shift Assay; Elements; Epigenetic Process; Eukaryota; Eukaryotic Cell; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genomics; Goals; Human Genome; In Vitro; Life; Link; Mediating; Methods; Modeling; Molecular Conformation; Nucleosomes; Pattern; Positioning Attribute; Protein p53; Proteins; Research; Role; Rotation; Set protein; Site; Structure; Surface; TP53 gene; Techniques; Testing; Work; chromatin modification; histone modification; human model; in vitro Assay; in vivo; interest; open source; programs; transcription factor; user-friendly; web server; web services

Project Summary: Uncovering a new role of nucleosomes in gene regulation Transcriptional factors (TFs) and nucleosomes are two major determinants for gene regulation in eukaryotic cells. Traditionally, TFs and nucleosomes are considered to be mutually exclusive. Recent studies have identified a growing list of proteins including the tumor suppressor p53 that are able to bind to nucleosomal DNA without disrupting the overall nucleosome structure. At least for these TFs, nucleosomes are no longer obstacles, and in some cases, nucleosomes can facilitate or even stabilize TF-DNA interactions. However, it was not clear if such interactions (between TFs and nucleosomes) have any biological significance. Our preliminary studies have shown that the extent of accessibility of p53 target sites in nucleosomes correlates with how p53 regulates its target genes, which highlights the importance of nucleosomes in mediating TF binding and controlling gene expression. The proposed research aims to gain full understanding of this new role of nucleosomes in gene regulation. In the Aim 1, we will focus on p53, intending to establish the link between accessibility of p53 binding sites in the context of chromatin and expression patterns of nearby genes. In the Aim 2, we will discover a comprehensive set of potential nucleosomal DNA-binding proteins in humans and model organisms. Nucleosome-TF interactions of interest will be validated by in vitro assays. At the conclusion of these studies, we will have re-defined the roles of nucleosomes in TF binding and gene regulation, developed theoretical and experimental method for testing nucleosome-TF interactions, and established a computational/experimental pipeline to identify nucleosomal DNA-binding proteins.

项目概述：揭示核小体在基因调控中的新作用

项目成果

Deep learning for histopathological segmentation of smooth muscle in the urinary bladder.

• DOI: 10.1186/s12911-023-02222-3
• 发表时间: 2023-07-15
• 期刊: BMC MEDICAL INFORMATICS AND DECISION MAKING
• 影响因子: 3.5
• 作者: Subramanya, Sridevi K.;Li, Rui;Wang, Ying;Miyamoto, Hiroshi;Cui, Feng
• 通讯作者: Cui, Feng

Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription.

染色质纤维的拓扑多样性：核小体重复长度，DNA连接数量和转录水平之间的相互作用。

• DOI: 10.3934/biophy.2015.4.613
• 发表时间: 2015
• 期刊: AIMS biophysics
• 影响因子: 1.5
• 作者: Norouzi D;Katebi A;Cui F;Zhurkin VB
• 通讯作者: Zhurkin VB

Predicting Biomedical Interactions With Higher-Order Graph Convolutional Networks.

• DOI: 10.1109/tcbb.2021.3059415
• 发表时间: 2022-03
• 期刊: IEEE/ACM transactions on computational biology and bioinformatics
• 作者: Kc K;Li R;Cui F;Haake AR
• 通讯作者: Haake AR

Vaccine candidate designed against carcinoembryonic antigen-related cell adhesion molecules using immunoinformatics tools.

• DOI: 10.1080/07391102.2020.1797539
• 发表时间: 2021-10
• 期刊: Journal of biomolecular structure & dynamics
• 影响因子: 4.4
• 作者: Gupta A;Rosato AJ;Cui F
• 通讯作者: Cui F

Cell type-specific transcriptome profiling in mammalian brains.

• DOI: 10.2741/4434
• 发表时间: 2016-06-01
• 期刊: Frontiers in bioscience (Landmark edition)
• 作者: LoVerso PR;Cui F
• 通讯作者: Cui F