OGT as a dosage sensor

OGT 作为剂量传感器

• 批准号: 10440360
• 负责人: ALMA L BURLINGAME
• 金额: $ 41.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440360
• 关键词: Active Sites; Affect; Alleles; Binding; Cell Count; Cells; Chromatin; Chromatin Remodeling Factor; Complex; Cues; Cytoplasmic Protein; Cytosine; DNA; DNA Methylation; DNA Modification Methylases; Data; Development; Dioxygenases; Diploidy; Dosage Compensation (Genetics); Dose; Embryo; Ensure; Enzymes; Epigenetic Process; Exhibits; Failure; Female; Future; Gene Dosage; Gene Expression; Genes; Genetic Transcription; Inner Cell Mass; Link; Mammals; Mediating; Messenger RNA; Mitochondrial Proteins; Modeling; Modification; Molecular; Mutation; Nuclear; Nuclear Proteins; Oxides; Peptides; Post-Translational Protein Processing; Production; Proteins; RNA; Regulation; Role; Signal Pathway; System; Testing; Transcript; Transferase; Untranslated RNA; Up-Regulation; X Chromosome; X Inactivation; XY females; demethylation; dosage; embryonic stem cell; fly; in vivo; insight; link protein; male; methyl group; mutant; oxidation; promoter; protein expression; recruit; response; sensor; stoichiometry; sugar; transcription factor; virtual

Project Summary Epigenetic regulators often lie downstream of signaling pathways that culminate in post-translational modifications, which affect their activity and ensure appropriate transcriptional responses to developmental and environmental cues. Our preliminary studies indicate that an interaction between epigenetic regulator, TET3, and an X-linked, post-translational modification enzyme, OGT, may be central in detecting X chromosome dosage and poising cells for X-inactivation. We propose to investigate the role of the TET3-OGT interaction in regulation of X chromosome inactivation, to obtain molecular insight into how cells count X chromosomes.

项目概要 表观遗传调节因子通常位于信号通路的下游，最终导致翻译后 修饰，影响其活性并确保对发育和发育产生适当的转录反应 环境线索。我们的初步研究表明，表观遗传调节因子 TET3、 X连锁翻译后修饰酶OGT可能是检测X染色体的核心 X 失活的剂量和平衡细胞。我们建议研究 TET3-OGT 相互作用在 X 染色体失活的调节，以获得细胞如何计数 X 染色体的分子洞察。