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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)766-772
Number of pages7
JournalNature Biotechnology
Volume37
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • Animals
  • Cell Line
  • DNA-Binding Proteins/metabolism
  • Gene Expression Regulation
  • Protein Binding
  • Single-Cell Analysis/methods
  • Transcriptome

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