Interpreting and Deploying Genomic Information During Animal Development

动物发育过程中基因组信息的解释和应用

• 批准号: 10810331
• 负责人: RICHARD S MANN
• 金额: $ 1.15万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-03 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10810331
• 关键词: Animals; Attention; Binding Sites; Cells; Code; DNA Binding; DNA Binding Domain; Defect; Development; Diabetes Mellitus; Embryonic Development; Family; Funding; Genes; Genetic Transcription; Genomics; Goals; HOX protein; Homeodomain Proteins; In Vitro; Invertebrates; Leg; Malignant Neoplasms; Mutation; Play; Post-Translational Protein Processing; Proteins; Resolution; Role; Specific qualifier value; Specificity; Vertebrates; Visualization; Wing; appendage; cofactor; experimental study; homeodomain; human disease; in vivo; member; mutant; novel; organ growth; programs; transcription factor; whole genome

Summary The long term goal of this project is to understand how members of large transcription factor families, which share a DNA binding domain and typically have very similar DNA binding specificities, execute highly specific functions in vivo. The primary focus of this proposal is on the Hox family of homeodomain transcription factors, which play critical roles during animal embryogenesis, organ development, and appendage specification in both vertebrates and invertebrates. When these transcription factors mis-regulate their target genes, either due to mutations in their protein-coding sequences or in their target DNA binding sites, developmental defects and many human diseases, from cancer to diabetes, can result. For the next funding period this project will bridge the gap between understanding how these factors specifically recognize their binding sites in vitro, often in conjunction with cofactors, and how they execute their specific functions in vivo. This will be accomplished using whole genome approaches with tagged and mutant Hox factors and by visualizing these proteins and their binding sites in living cells. Additional efforts will be to identify and characterize newly discovered novel cofactors and mechanisms, such as post-translational modifications of Hox proteins, that can alter their DNA binding specificities and/or transcriptional regulatory activities in vivo. In all cases, these experiments will be grounded in identifying and understanding how Hox proteins regulate their bona fide target genes, which allow them to orchestrate entire developmental programs, such as the development of legs and wings.

总结

项目成果

SpyChIP identifies cell type-specific transcription factor occupancy from complex tissues.

• DOI: 10.1073/pnas.2122900119
• 发表时间: 2022-06-21
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

Fluorescent labeling of genomic loci in Drosophila imaginal discs with heterologous DNA-binding proteins.

• DOI: 10.1016/j.crmeth.2022.100175
• 发表时间: 2022-03-28
• 期刊: Cell reports methods

Homothorax controls a binary Rhodopsin switch in Drosophila ocelli.

• DOI: 10.1371/journal.pgen.1009460
• 发表时间: 2021-07
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Mishra AK;Fritsch C;Voutev R;Mann RS;Sprecher SG
• 通讯作者: Sprecher SG

Divergent expression of paralogous genes by modification of shared enhancer activity through a promoter-proximal silencer.

• DOI: 10.1016/j.cub.2022.06.069
• 发表时间: 2022-08-22
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Loker, Ryan;Mann, Richard S.
• 通讯作者: Mann, Richard S.

Robust ΦC31-Mediated Genome Engineering in Drosophila melanogaster Using Minimal attP/attB Phage Sites.

• DOI: 10.1534/g3.118.200051
• 发表时间: 2018-05-04
• 期刊: G3 (Bethesda, Md.)
• 作者: Voutev R;Mann RS
• 通讯作者: Mann RS