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

Koos Rooijers, Corina M Markodimitraki, Franka J Rang, Sandra S de Vries, Alex Chialastri, Kim L de Luca, Dylan Mooijman, Siddharth S Dey, Jop Kind

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)766-772
Aantal pagina's7
TijdschriftNature Biotechnology
Volume37
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - jul 2019

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