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Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells
- Source :
- Nature Biotechnology, Nature Biotechnology, 37(7), 766-772. Nature Publishing Group, Nature biotechnology
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- The epigenome plays a critical role in regulating gene expression in mammalian cells. However, understanding how cell-to-cell heterogeneity in the epigenome influences gene expression variability remains a major challenge. Here we report a novel method for simultaneous single-cell quantification of protein-DNA contacts with DamID and transcriptomics (scDamID&T). This method enables quantifying the impact of protein-DNA contacts on gene expression from the same cell. By profiling lamina-associated domains (LADs) in human cells, we reveal different dependencies between genome-nuclear lamina (NL) association and gene expression in single cells. In addition, we introduce the E. coli methyltransferase, Dam, as an in vivo marker of chromatin accessibility in single cells and show that scDamID&T can be utilized as a general technology to identify cell types in silico while simultaneously determining the underlying gene-regulatory landscape. With this strategy the effect of chromatin states, transcription factor binding, and genome organization on the acquisition of cell-type specific transcriptional programs can be quantified.
- Subjects :
- Cell type
Methyltransferase
In silico
Cell
Biomedical Engineering
Bioengineering
Computational biology
Biology
Applied Microbiology and Biotechnology
Article
Cell Line
Transcriptome
chemistry.chemical_compound
03 medical and health sciences
0302 clinical medicine
Gene expression
medicine
Animals
Transcription factor
030304 developmental biology
Genomic organization
Regulation of gene expression
0303 health sciences
DNA-Binding Proteins/metabolism
Single-Cell Analysis/methods
Epigenome
Embryonic stem cell
Cell biology
Chromatin
DNA-Binding Proteins
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Molecular Medicine
Single-Cell Analysis
DNA
030217 neurology & neurosurgery
Protein Binding
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 10870156
- Database :
- OpenAIRE
- Journal :
- Nature Biotechnology, Nature Biotechnology, 37(7), 766-772. Nature Publishing Group, Nature biotechnology
- Accession number :
- edsair.doi.dedup.....2a8e0da19aac235727c5f00131f08a14
- Full Text :
- https://doi.org/10.1101/529388