Integrative analysis of single-cell expression data reveals distinct regulatory states in bidirectional promoters

  • Background: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs. Results: We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles. Conclusions: Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.

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Author:Fatemeh Behjati Ardakani, Kathrin Kattler, Karl NordströmORCiD, Nina Gasparoni, Gilles GasparoniORCiDGND, Sarah Fuchs, Anupam Sinha, Matthias Barann, Peter Ebert, Jonas Fischer, Barbara Hutter, Gideon Zipprich, Charles D. Imbusch, Bärbel Felder, Jürgen Eils, Benedikt Brors, Thomas Lengauer, Thomas Manke, Philip Rosenstiel, Jörn Walter, Marcel Holger SchulzORCiDGND
Pubmed Id:
Parent Title (English):Epigenetics & chromatin
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/11/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/12/06
Tag:Bidirectional genes; Epigenetics; Single-cell RNA-seq
Issue:1, Art. 66
Page Number:14
First Page:1
Last Page:14
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0