Olfactory receptor mRNAs as lncRNAs that regulate genomic interactions
嗅觉受体 mRNA 作为调节基因组相互作用的 lncRNA
基本信息
- 批准号:10376032
- 负责人:
- 金额:$ 48.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAdaptor Signaling ProteinAffectAllelesArchitectureBindingBinding ProteinsBiochemicalChromatinChromosome StructuresCodeComplexDataDevelopmentDevelopmental ProcessEnhancersEnvironmentEpigenetic ProcessFeedbackGene ClusterGene ExpressionGene FamilyGenerationsGeneticGenetic Enhancer ElementGenetic TranscriptionGenomicsGreekHumanIn SituIslandLightLinkMediatingMessenger RNAMolecularMusNeurodevelopmental DisorderNeuronal DifferentiationNuclearNuclear ProteinsOlfactory PathwaysOther GeneticsPhasePhase TransitionProcessProductionPropertyProteinsRNARNA-Binding ProteinsReceptor GeneRegulationRegulator GenesReportingRepressionRoleSignal TransductionSpecificityStructureSystemTranscriptional RegulationUntranslated RNAYeastsexperimental studygene translocationgenetic approachgenomic locusin vivoinsightinterdisciplinary approachnerve stem cellnovelolfactory receptorolfactory sensory neuronsprogramspromoterreceptor expressionrecruittranscription factor
项目摘要
Abstract
The monogenic, monoallelic, and seemingly stochastic transcriptional choice of one out of > 1000 olfactory
receptor (OR) genes remained elusive for decades after the discovery of the largest mammalian gene family.
However, in the past few years we obtained significant understanding on the molecular underpinnings of this
enigmatic gene regulatory process. Specifically, we showed that OR gene clusters become heterochromatic at
the early stages of olfactory sensory neuron (OSN) differentiation and then they aggregate in distinct nuclear
compartments that assure their stable repression. As a result of this interchromosomal convergence, intergenic
OR enhancers (known as Greek Islands) that are found in most OR gene clusters come in close nuclear
proximity and form a multi-chromosomal super-enhancer that in each OSN associates with the transcriptionally
active OR allele. The formation of the Greek Island hub is dependent upon the recruitment of the adaptor
protein Ldb1, which is essential for the stable interchromosomal interactions between Greek Islands and for
OR transcription. This intricate network of activating and repressive interchromosomal interactions, together
with a feedback signal elicited by the expression of the chosen OR, likely generate the regulatory framework
for transcriptional singularity. However, what remains unknown is the process by which an OR allele is
recruited to the Greek Island hub and the mechanism that assures that only one OR allele will remain stably
associated with a multi-chromosomal structure that contains numerous enhancer elements. Our preliminary
data suggest that developmentally transient OR transcription and production of nascent OR mRNAs contribute
to the recruitment of an OR allele to the Greek Island hub and to OR gene choice. Thus, we propose genetic
experiments that will determine which sequences of the sense OR mRNA are required and sufficient for
recruitment of trans OR enhancers, what proteins recognized the nascent OR mRNA and what contribution
these proteins have to the assembly of a multi-enhancer/OR complex. These experiments not only will shed
light to the enigmatic process of OR gene choice, but will also provide general molecular principles for the
mechanisms that mediate genomic compartmentalization during cellular differentiation.
摘要
项目成果
期刊论文数量(0)
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Stavros Lomvardas其他文献
Stavros Lomvardas的其他文献
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{{ truncateString('Stavros Lomvardas', 18)}}的其他基金
The "olfactosome" as a biomolecular condensate
作为生物分子凝聚物的“嗅觉体”
- 批准号:
10669291 - 财政年份:2022
- 资助金额:
$ 48.05万 - 项目类别:
Principles of zonal olfactory receptor gene expression
带状嗅觉受体基因表达原理
- 批准号:
10350605 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Interrogating genome folding trajectories in health and disease
探究健康和疾病中的基因组折叠轨迹
- 批准号:
10473744 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Olfactory receptor mRNAs as lncRNAs that regulate genomic interactions
嗅觉受体 mRNA 作为调节基因组相互作用的 lncRNA
- 批准号:
10614532 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Principles of zonal olfactory receptor gene expression
带状嗅觉受体基因表达原理
- 批准号:
10570848 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Interrogating genome folding trajectories in health and disease
探究健康和疾病中的基因组折叠轨迹
- 批准号:
10685554 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Deciphering mechanisms of COVID-19 induced anosmia
解读 COVID-19 引起的嗅觉丧失的机制
- 批准号:
10176800 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Non-cell autonomous disruption of genomic interactions as a cause of dementia
基因组相互作用的非细胞自主破坏是痴呆的原因
- 批准号:
10712217 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Interrogating genome folding trajectories in health and disease
探究健康和疾病中的基因组折叠轨迹
- 批准号:
10266185 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别:
Interrogating genome folding trajectories in health and disease
探究健康和疾病中的基因组折叠轨迹
- 批准号:
10117398 - 财政年份:2020
- 资助金额:
$ 48.05万 - 项目类别: