Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells.
Nat Biotechnol
; 37(7): 766-772, 2019 07.
Article
in En
| MEDLINE
| ID: mdl-31209373
ABSTRACT
Protein-DNA interactions are critical to the regulation of gene expression, but it remains challenging to define how cell-to-cell heterogeneity in protein-DNA binding influences gene expression variability. Here we report a method for the simultaneous quantification of protein-DNA contacts by combining single-cell DNA adenine methyltransferase identification (DamID) with messenger RNA sequencing of the same cell (scDam&T-seq). We apply scDam&T-seq to reveal how genome-lamina contacts or chromatin accessibility correlate with gene expression in individual cells. Furthermore, we provide single-cell genome-wide interaction data on a polycomb-group protein, RING1B, and the associated transcriptome. Our results show that scDam&T-seq is sensitive enough to distinguish mouse embryonic stem cells cultured under different conditions and their different chromatin landscapes. Our method will enable the analysis of protein-mediated mechanisms that regulate cell-type-specific transcriptional programs in heterogeneous tissues.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Single-Cell Analysis
/
Transcriptome
Limits:
Animals
Language:
En
Journal:
Nat Biotechnol
Journal subject:
BIOTECNOLOGIA
Year:
2019
Type:
Article
Affiliation country:
Netherlands