Natural genetic variation impacts expression levels of coding, non‐coding, and antisense transcripts in fission yeast

Molecular Systems Biology

Mathieu Clément-Ziza¹  Francesc X Marsellach⁴  Sandra Codlin⁴  Manos A Papadakis²  Susanne Reinhardt¹  María Rodríguez-López⁴  Stuart Martin⁴  Samuel Marguerat⁴  Alexander Schmidt³  Eunhye Lee⁴  Christopher T Workman²  Jürg Bähler⁴ 

[1]Biotechnology Centre, Technische Universität Dresden, Dresden, Germany

[2]Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark

[3]Biozentrum, University of Basel, Basel, Switzerland

[4]Department of Genetics, Evolution & Environment and UCL Genetics Institute, University College London, London, UK

关键词: antisense transcription;    histone variant;    non‐coding RNA;    QTL;    Schizosaccharomyces pombe;   

DOI  :  10.15252/msb.20145123

来源: Wiley

【 摘 要 】

Abstract

Our current understanding of how natural genetic variation affects gene expression beyond well-annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the potential to close this gap. Here, we generated the first recombinant strain library for fission yeast and conducted an RNA-seq-based QTL study of the coding, non-coding, and antisense transcriptomes. We show that the frequency of distal effects (trans-eQTLs) greatly exceeds the number of local effects (cis-eQTLs) and that non-coding RNAs are as likely to be affected by eQTLs as protein-coding RNAs. We identified a genetic variation of swc5 that modifies the levels of 871 RNAs, with effects on both sense and antisense transcription, and show that this effect most likely goes through a compromised deposition of the histone variant H2A.Z. The strains, methods, and datasets generated here provide a rich resource for future studies.

Synopsis

A large-scale eQTL study of coding, non-coding, and antisense transcripts, performed using a recombinant fission yeast strain library, reveals the prevalence of trans-eQTLs and identifies a variant affecting thousands of expression traits, presumably via epigenetic modification.

• A fission yeast strain library suitable for quantitative trait locus (QTL) analyses is generated and characterized.
• A QTL analysis of sense, antisense, coding, and non-coding expression as well as growth traits is performed.
• Non-coding genes are subject to eQTL control as much as coding genes.
• Trans-eQTLs are far more abundant than cis-eQTLs.
• A swc5 variant impacting thousands of sense and antisense traits, presumably through epigenetic modification (H2A.Z occupancy), is identified.

【 授权许可】

CC BY   
© 2014 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.