A transposase system for integrative ChIP-exo and ATAC-seq analysis at single-cell resolution
用于单细胞分辨率综合 ChIP-exo 和 ATAC-seq 分析的转座酶系统
基本信息
- 批准号:10210424
- 负责人:
- 金额:$ 48.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-14 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAdultAutomationBar CodesBindingBiological AssayCellsChIP-seqChromatinCodeComplexDNADNA FragmentationDNA SequenceDataData AnalysesDevelopmentDiagnosticDigestionDiseaseEmbryoEvolutionExonucleaseGenetic TranscriptionGenomeGenomic LibraryGenomicsGoalsHumanIndividualLibrariesLigationMeasurementMeasuresMusMutationNucleotidesPatientsPreventive MedicineProtocols documentationPublic HealthResearchResolutionRoboticsSamplingSingle-Stranded DNASourceSystemTechnologyTimeTissuesTn5 transposaseTransposaseVariantWorkbasebiological systemscell typecombinatorialdesignembryonic stem cellexperimental studyhuman diseaseimprovedin vivoinnovationinsightinternal controlnew technologynovel strategiespluripotencytheoriestranscription factor
项目摘要
PROJECT SUMMARY
Predicting cis-regulatory information from sequence alone is not yet possible, but collecting cis-regulatory
information systematically across all human cell types and across species would be feasible with significant
progress in technology. Here we propose to develop such breakthrough technology that will allow to extract
cis-regulatory information from any cell type, including mixtures of heterogeneous cell types. The technology is
based on a transposase system that combines ChIP and ATAC-seq technology, and thus allows the
simultaneous measurement of chromatin accessibility and transcription factor occupancy in the same cells. It is
innovative in its orders of magnitude improvement in efficiency by which DNA fragments enter the genomic
library, which allows the assay to be performed at single-cell resolution. It is cutting-edge in its resolution,
which allows the identification of precise footprints of transcription factor bound in vivo. We will optimize scale
and workflow, as well as develop an initial analysis framework, to make the technology applicable to a wide
range of systems. As proof-of-principle, we will apply the technology to early mouse embryos and compare the
results to those obtained from mouse embryonic stem cells. Having such technology will open the door to
unprecedented explorations of cis-regulatory information across any cell type. It will deepen our understanding
of transcriptional regulatory networks during development and evolution, and will provide insights into
mutations and mechanisms underlying human disease.
项目摘要
仅从序列预测顺式调节信息尚不可能,但收集顺式调节信息
跨所有人类细胞类型和跨物种的系统信息将是可行的,
技术进步。在这里,我们建议开发这样的突破性技术,将允许提取
来自任何细胞类型的顺式调节信息,包括异质细胞类型的混合物。该技术
基于结合ChIP和ATAC-seq技术的转座酶系统,从而允许
同时测量同一细胞中的染色质可及性和转录因子占有率。是
在其数量级上的创新性提高了DNA片段进入基因组的效率
库,其允许以单细胞分辨率进行测定。它的分辨率很高,
其允许鉴定体内结合的转录因子的精确足迹。我们将优化规模
和工作流程,以及开发一个初步的分析框架,使该技术适用于广泛的
系统的范围。作为原理证明,我们将把这项技术应用于早期小鼠胚胎,
从小鼠胚胎干细胞中获得的结果。拥有这样的技术将打开大门,
这是对任何细胞类型的顺式调节信息的前所未有的探索。它会加深我们的理解
转录调控网络在发展和进化过程中,并将提供见解,
突变和人类疾病的潜在机制。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Seven myths of how transcription factors read the cis-regulatory code.
- DOI:10.1016/j.coisb.2020.08.002
- 发表时间:2020-10
- 期刊:
- 影响因子:3.7
- 作者:Zeitlinger J
- 通讯作者:Zeitlinger J
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