Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells

TY - JOUR

T1 - Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells

AU - Rooijers, Koos

AU - Markodimitraki, Corina M

AU - Rang, Franka J

AU - de Vries, Sandra S

AU - Chialastri, Alex

AU - de Luca, Kim L

AU - Mooijman, Dylan

AU - Dey, Siddharth S

AU - Kind, Jop

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - DNA-Binding Proteins/metabolism

KW - Gene Expression Regulation

KW - Protein Binding

KW - Single-Cell Analysis/methods

KW - Transcriptome

U2 - 10.1038/s41587-019-0150-y

DO - 10.1038/s41587-019-0150-y

M3 - Article

C2 - 31209373

SN - 1087-0156

VL - 37

SP - 766

EP - 772

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 7

ER -