Control mechanisms of 5-hydroxymethylcytosine metabolism in human cells
人体细胞5-羟甲基胞嘧啶代谢的控制机制
基本信息
- 批准号:10629908
- 负责人:
- 金额:$ 13.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AttentionBase Excision RepairsBiological AssayBiomedical ResearchBloodBrainCRISPR/Cas technologyCell LineCell physiologyCellsCpG dinucleotideCytosineDNADNA DamageDNA Double Strand BreakDNA MethylationDNA Modification MethylasesDNA RepairDNA biosynthesisDNA lesionDevelopmentDiseaseEnzymesEpigenetic ProcessFamilyFunctional disorderGene Expression RegulationGenerationsGenesGenetic TranscriptionGenomeGenome StabilityGlioblastomaGoalsHumanInduced pluripotent stem cell derived neuronsKnowledgeLightLinkLymphomaMalignant NeoplasmsMass Spectrum AnalysisMeasuresMediatingMetabolismMethylationMitoticModelingNeurodegenerative DisordersNeuronsNuclearNucleotidesOrganOrganismOutcomePathway interactionsPluripotent Stem CellsProcessProductionProteinsResistanceRoleSiteSurvival RateSystemTechniquesTestingThymine DNA GlycosylaseTimeTissue-Specific Gene ExpressionTissuesage relatedanti-cancer therapeuticcell typeconditional knockoutdemethylationdrug discoveryepigenetic markerepigenetic regulationhigh throughput screeninghuman DNAhuman diseaseknock-downmortalitynovelnovel markernovel therapeuticsoxidationpostmitoticrepairedresponsetranslocasetumor progression
项目摘要
Project Summary
The 5-hydroxymethylcytosine (5hmC) in mammalian DNA is drawing significant attention in epigenetics
because of its indispensable roles in gene expression regulation. The loss of 5hmCs in various cancers
including glioblastomas and lymphomas has been linked to the poor survival rate as well as the resistance to
anti-cancer therapeutics. Although there is amassing evidence of 5hmCs as a novel epigenetic marker, there is
very little understanding on how 5hmCs are enriched at specific loci in the genome. In this project, we aim to
identify the factors controlling the DNA demethylation pathway, which result in the formation of locus-specific
5hmCs in human neurons. For this purpose, proteins controlling the activity of ten-eleven translocase (TET)
family enzymes in the DNA demethylation pathway will be identified. To examine the function of candidate
proteins, we will take advantage of human induced-neurons (hiNs) derived from human induced-pluripotent
stem cells (hiPSCs). In addition, we will elucidate the role and fate of 5hmCs formed during DNA damage
repair process using blue light-inducible CRISPR/Cas9 technique. This robust experimental platform will
enable the rapid production of isogenic and homogenous neurons and other cell types. With this cell-based
assay system, high-throughput assays can be developed that will advance biomedical researches and drug
discoveries. Finally, we expect the successful completion of this project will expand our understanding on DNA
demethylation and their roles in epigenetics, development, and various human diseases.
项目总结
项目成果
期刊论文数量(0)
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