Loss of transcriptional homeostasis of genes lacking CpG islands during aging
衰老过程中缺乏 CpG 岛的基因转录稳态丧失
基本信息
- 批准号:10488179
- 负责人:
- 金额:$ 47.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-15 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAgeAge of OnsetAgingArchitectureAutomobile DrivingBromodomainCaenorhabditis elegansCardiomyopathiesCell AgingCell NucleusCellsChromatinChronicComputer AnalysisCpG IslandsDataDeteriorationDevelopmentDiseaseEchocardiographyElementsExhibitsFunctional disorderGene ExpressionGene SilencingGenesGenetic TranscriptionHeartHeterochromatinHistologyHomeostasisHumanImmuneImmunofluorescence ImmunologicInflammationInflammatoryLongevityMediatingMusNoiseNuclearNuclear LaminaOncogene DeregulationOrganPathologyPatternPharmacologyPhysiologicalPlasmaPremature aging syndromeProtein FamilyProteomePulmonary FibrosisRNAReportingResearchStrokeSystemTestingTimeTissuesage relatedagedcytokinedrug repurposingfrailtyin silicoindexinginhibitorinnovationischemic cardiomyopathymRNA sequencingmouse modelnovelpromotersingle-cell RNA sequencingsystemic inflammatory responsetherapeutically effective
项目摘要
PROJECT SUMMARY/ABSTRACT
Changes in chromatin architecture is a hallmark of aging. Disruption of the nuclear lamina and associated
heterochromatin are commonly observed in various aging contexts, including premature aging diseases, cellular
senescence, and normative aging. Although these shared structural changes have been reported for over two
decades, their impact on transcription and the contribution to age-related degenerative changes remains
unknown. Through computational analysis, we recently identified that CpG islands (CGIs), mammalian
promoter-associated elements, provide important clues to answering this question. In humans, about 60% of
genes contain CGIs at their promoters (CGI+ genes) and are broadly expressed throughout the body, while the
other 40% of genes that do not have CGIs (CGI- genes) exhibit tissue-restricted expression patterns. Our
preliminary results demonstrate that, in young nuclei, only CGI- genes can reside within lamina-associated
heterochromatin, when transcriptionally inactive. This suggests that aging-mediated heterochromatin
decondensation and lamina disruption would specifically hinder the repressive status of CGI- genes. Our data
indeed show over 30% of CGI- genes are mis-activated within various aged tissues, and this pattern coincides
with the loss of organ function. In this project, we will test the novel hypothesis that 1) changes in chromatin
architecture during aging directly trigger uncontrolled expression of CGI- genes in tissues/contexts where they
should not be expressed and this, in turn, 2) accelerates age-associated deterioration. We will also test whether
the 3) pharmacological inhibition of CGI- gene misexpression delay age-related degenerative changes.
项目总结/文摘
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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Samuel Beck其他文献
Samuel Beck的其他文献
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{{ truncateString('Samuel Beck', 18)}}的其他基金
Chromatin architecture disruption and the vicious cycle of aging.
染色质结构破坏和衰老的恶性循环。
- 批准号:
10901040 - 财政年份:2023
- 资助金额:
$ 47.02万 - 项目类别:
Loss of transcriptional homeostasis of genes lacking CpG islands during aging
衰老过程中缺乏 CpG 岛的基因转录稳态丧失
- 批准号:
10814562 - 财政年份:2023
- 资助金额:
$ 47.02万 - 项目类别:
Loss of transcriptional homeostasis of genes lacking CpG islands during aging
衰老过程中缺乏 CpG 岛的基因转录稳态丧失
- 批准号:
10209189 - 财政年份:2021
- 资助金额:
$ 47.02万 - 项目类别:
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