Origin firing at repetitive sequences and genome replication - Admin Supplement
重复序列和基因组复制的起源 - 管理补充
基本信息
- 批准号:10626663
- 负责人:
- 金额:$ 0.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-02-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AffectAgingBiological PhenomenaCell AgingChromatinChromosome StructuresCopperDNA Polymerase IIDNA SequenceGenesGenetic TranscriptionGenomeHeterochromatinHuman GenomeLinkLocationMediatingMethodsModelingModernizationMutationNucleosomesNucleotidesPeptide Initiation FactorsPositioning AttributePre-Replication ComplexPrevalenceProcessRNARepetitive SequenceReplication InitiationReplication OriginRepressionResourcesRestRibosomal DNASaccharomycetalesSiteSpecificitySystemTestingTranscriptional ActivationYeastsbasecarcinogenesisdeep sequencingdensityenvironmental changeepigenomeparent grantparent projecttool
项目摘要
Abstract of the Parent Grant (R01 GM117446)
Over half of the human genome is comprised of repetitive DNA sequences
organized as gene-poor, late replicating, transcriptionally silent heterochromatin.
Recent studies have discerned widespread transcriptional de-repression at repeated
regions during carcinogenesis and aging. De-repression accelerates replication of these
regions and thus compromises replication in the gene-rich transcriptionally active
chromatin. Despite the importance and prevalence of the association between low levels
of transcription and late replication, the mechanistic basis for this link remains unclear.
The ribosomal DNA (rDNA) as well as copper-inducible CUP1 arrays in
budding yeast are ideal experimental systems in which to elucidate these mechanisms
for two main reasons. First, at each locus, a single manipulation, Sir2 depletion at the
rDNA, and cooper administration at the CUP1, activates both transcription and
replication, providing a simple tool to manipulate both processes. Second, each rDNA
and CUP1 repeat features a single, sequence-defined origin of replication, which creates
uniform and predictable positioning of replication initiation factors and nucleosomes in
their vicinity. This feature makes these systems, and yeast origins in general, ideal for
the application of deep sequencing methods for epigenome profiling we have
developed, offering a tremendous advantage over mammalian origins whose lack of
sequence-specificity confounds modern deep sequencing-based approaches.
Our methods resolves at nucleotide level the precise location of nucleosomes and pre-
replicative complexes (pre-RC) at the repetitive as well as in unique regions of the
genome. Using these methods, we discovered that transcriptional activation at both
rDNA and CUP1 origins leads to reduced occupancy of nucleosomes adjacent to pre-
RC, though by different means at the two loci: At CUP1, transcription reduces
nucleosome occupancy next to the pre-RC loading site, whereas at the rDNA the
nucleosome occupancy next to the pre-RC loading site does not change; instead, RNA
Pol-II pushes pre-RC to an adjacent region with low nucleosome density. Using this
experimental system and the tools for chromatin profiling we have developed, we will
determine whether high nucleosome occupancy adjacent to pre-RC inhibits replication
initiation and whether chromatin compaction-mediated inhibition of nucleosome
remodelers enforce late replication in transcriptionally silent chromatin.
家长补助金摘要(R01 GM117446)
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Antonio Bedalov其他文献
Antonio Bedalov的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Antonio Bedalov', 18)}}的其他基金
MeCP2 reactivation from the inactive X chromosome as treatment for Rett syndrome
从失活的 X 染色体重新激活 MeCP2 作为雷特综合征的治疗方法
- 批准号:
10826905 - 财政年份:2023
- 资助金额:
$ 0.8万 - 项目类别:
Origin firing at repetitive sequences and genome replication
重复序列和基因组复制的起源
- 批准号:
10356149 - 财政年份:2016
- 资助金额:
$ 0.8万 - 项目类别:
Origin firing at repetitive sequences and genome replication
重复序列和基因组复制的起源
- 批准号:
10651624 - 财政年份:2016
- 资助金额:
$ 0.8万 - 项目类别:
SIRT2 Inhibitors for the Treatment of B-cell Lymphoma
SIRT2 抑制剂用于治疗 B 细胞淋巴瘤
- 批准号:
9197069 - 财政年份:2016
- 资助金额:
$ 0.8万 - 项目类别:
SIRT2 Inhibitors for the Treatment of B-cell Lymphoma
SIRT2 抑制剂用于治疗 B 细胞淋巴瘤
- 批准号:
10602858 - 财政年份:2016
- 资助金额:
$ 0.8万 - 项目类别:
Origin firing at repetitive sequences and genome replication
重复序列和基因组复制的起源
- 批准号:
9008959 - 财政年份:2016
- 资助金额:
$ 0.8万 - 项目类别:
Protein Biomarkers in Childhood Acute Myeloid Leukemia
儿童急性髓系白血病的蛋白质生物标志物
- 批准号:
8227276 - 财政年份:2012
- 资助金额:
$ 0.8万 - 项目类别:
Protein Biomarkers in Childhood Acute Myeloid Leukemia
儿童急性髓系白血病的蛋白质生物标志物
- 批准号:
8435374 - 财政年份:2012
- 资助金额:
$ 0.8万 - 项目类别:
Development of cambinol analogues as antilymphoma agents
作为抗淋巴瘤药物的 Cambinol 类似物的开发
- 批准号:
7768411 - 财政年份:2008
- 资助金额:
$ 0.8万 - 项目类别:
Development of cambinol analogues as antilymphoma agents
作为抗淋巴瘤药物的 Cambinol 类似物的开发
- 批准号:
8230766 - 财政年份:2008
- 资助金额:
$ 0.8万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Collaborative R&D
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Operating Grants
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Studentship
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Standard Grant
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Fellowship Award
虚弱高齢者のSuccessful Agingを支える地域課題分析指標と手法の確立
建立区域问题分析指标和方法,支持体弱老年人成功老龄化
- 批准号:
23K20355 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
「ケア期間」に着目したbiological aging指標の開発
开发聚焦“护理期”的生物衰老指数
- 批准号:
23K24782 - 财政年份:2024
- 资助金额:
$ 0.8万 - 项目类别:
Grant-in-Aid for Scientific Research (B)