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


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.

SUBMITTER: Rooijers K 

PROVIDER: S-EPMC6609448 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Rooijers Koos K   Markodimitraki Corina M CM   Rang Franka J FJ   de Vries Sandra S SS   Chialastri Alex A   de Luca Kim L KL   Mooijman Dylan D   Dey Siddharth S SS   Kind Jop J  

Nature biotechnology 20190617 7


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 chromati  ...[more]

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