PT  - JOURNAL ARTICLE
AU  - Koos Rooijers
AU  - Corina M. Markodimitraki
AU  - Franka J. Rang
AU  - Sandra S. de Vries
AU  - Alex Chialastri
AU  - Kim de Luca
AU  - Dylan Mooijman
AU  - Siddharth S. Dey
AU  - Jop Kind
TI  - Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells
AID  - 10.1101/529388
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 529388
4099  - http://biorxiv.org/content/early/2019/01/24/529388.short
4100  - http://biorxiv.org/content/early/2019/01/24/529388.full
AB  - The epigenome plays a critical role in regulating gene expression in mammalian cells. However, understanding how cell-to-cell heterogeneity in the epigenome influences gene expression variability remains a major challenge. Here we report a novel method for simultaneous single-cell quantification of protein-DNA contacts with DamID and transcriptomics (scDamID&T). This method enables quantifying the impact of protein-DNA contacts on gene expression from the same cell. By profiling lamina-associated domains (LADs) in human cells, we reveal different dependencies between genome-nuclear lamina (NL) association and gene expression in single cells. In addition, we introduce the E. coli methyltransferase, Dam, as an in vivo marker of chromatin accessibility in single cells and show that scDamID&T can be utilized as a general technology to identify cell types in silico while simultaneously determining the underlying gene-regulatory landscape. With this strategy the effect of chromatin states, transcription factor binding, and genome organization on the acquisition of cell-type specific transcriptional programs can be quantified.