Deciphering the mechanism of long-range gene regulation in vivo
破译体内长程基因调控机制
基本信息
- 批准号:10473041
- 负责人:
- 金额:$ 141.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-09 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAffectBase PairingBinding ProteinsChromatinCommunicationDNADevelopmentDiseaseDistantElementsEnhancersFoundationsGene ExpressionGene Expression ProfileGene Expression RegulationGene Transfer TechniquesGenesGenetic TranscriptionGenomeGenomicsHuman GenomeImaging technologyKnowledgeLinkMapsMediatingMethodsMusMutationNucleotidesPathologicRegulationRegulatory ElementReporterResolutionRoleTechnologyTimeUntranslated RNAVariantWorkgain of functiongenetic regulatory proteingenome editinghuman diseasein vivointerdisciplinary approachnovelpromoterremote controltranscription factor
项目摘要
PROJECT SUMMARY
Distant-acting (“remote”) transcriptional enhancers bound by transcription factors (TFs) drive gene expression
patterns in space and time. The importance of this function is underscored by mounting evidence linking
mutations affecting remote enhancers to human disease. What remains unclear is how these remote enhancers
regulate their target genes over long genomic distances, often skipping intervening genes. Remote enhancers
typically interact with target promoters with the support of higher-order chromatin organization, but disruption of
this chromatin organization does not abolish enhancer–promoter interactions. What additional factors regulate
these long-range regulatory interactions remains largely unexplored. To address this central question, the
proposed project will use a novel gain-of-function approach to identify cis-regulatory sequences that mediate
long-range enhancer–promoter communication in the context of mammalian development. Traditional methods
that assess in vivo enhancer activity rely on enhancer-reporter transgenesis; however, technical limitations
preclude this approach from assessing long-range enhancer activity. The proposed work overcomes this
limitation by utilizing efficient enhancer replacement technology in mice to systematically characterize in vivo
long-range enhancer activity and identify cis-regulatory sequences that are critical for this long-range activity. To
determine the mechanism of long-range regulation by these remote control elements and identify regulatory
proteins that bind them, this work will use a multidisciplinary approach to map and visualize enhancer–promoter
contacts at macromolecular resolution. Functional characterization of remote control elements will expand the
repertoire of known cis-regulatory elements, provide a novel general mechanism for long-range enhancer–
promoter communication, and substantially advance knowledge of the role of 3D-genome organization in the
context of development and disease.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Evgeny Kvon其他文献
Evgeny Kvon的其他文献
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{{ truncateString('Evgeny Kvon', 18)}}的其他基金
Functional assessment of enhancer-gene interactions in vivo
体内增强子-基因相互作用的功能评估
- 批准号:
10331859 - 财政年份:2020
- 资助金额:
$ 141.3万 - 项目类别:
Functional assessment of enhancer-gene interactions in vivo
体内增强子-基因相互作用的功能评估
- 批准号:
9545036 - 财政年份:2017
- 资助金额:
$ 141.3万 - 项目类别:
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