Divergent transcription is associated with promoters of transcriptional regulators

Cyrille Lepoivre,Ivo Gut,Jean Imbert,Jean-Christophe Andrau,Muhammad Ahmad Maqbool,Salvatore Spicuglia,Denis Puthier,Marta Gut,Joaquin Zacarias-Cabeza,Laurent Vanhille,Hélène Holota,Mohamed Belhocine,Romain Fenouil,Marc-Antoine Garibal,Miriam Yammine,Frederic Koch,Beatrice Loriod,Aurélie Bergon,Aurélien Griffon

doi:10.1186/1471-2164-14-914

Abstract

BackgroundDivergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Moreover, many described long non-coding RNAs (lncRNAs) are transcribed antisense from coding gene promoters. However, the general significance of divergent lncRNA/mRNA gene pair transcription is still poorly understood. Here, we used strand-specific RNA-seq with high sequencing depth to thoroughly identify antisense transcripts from coding gene promoters in primary mouse tissues.ResultsWe found that a substantial fraction of coding-gene promoters sustain divergent transcription of long non-coding RNA (lncRNA)/mRNA gene pairs. Strikingly, upstream antisense transcription is significantly associated with genes related to transcriptional regulation and development. Their promoters share several characteristics with those of transcriptional developmental genes, including very large CpG islands, high degree of conservation and epigenetic regulation in ES cells. In-depth analysis revealed a unique GC skew profile at these promoter regions, while the associated coding genes were found to have large first exons, two genomic features that might enforce bidirectional transcription. Finally, genes associated with antisense transcription harbor specific H3K79me2 epigenetic marking and RNA polymerase II enrichment profiles linked to an intensified rate of early transcriptional elongation.ConclusionsWe concluded that promoters of a class of transcription regulators are characterized by a specialized transcriptional control mechanism, which is directly coupled to relaxed bidirectional transcription.

Highlights

Divergent transcription is a wide-spread phenomenon in mammals
Systematic identification of genes associated with long upstream antisense transcripts We sought to assess whether production of long antisense transcripts is a general feature of mammalian gene promoters
Using a stringent threshold (p < 0.005; see Methods) we found 6.8% (1,177) of coding RefSeq transcripts to be associated with long upstream antisense transcripts, of which 236 overlap with previously annotated non-coding transcripts

Summary

Introduction

Short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Recent findings have shown that some antisense transcripts act as epigenetic regulators of gene expression and chromatin remodeling [8], while others play a role at the level of translation efficiency [10]. Besides these transcripts, the existence of non-coding antisense transcripts emanating from the promoters of protein-coding genes (i.e. headto-head conformation) has emerged as a widespread phenomenon from yeast to mammals [11]. Whether long antisense transcripts emanating from bidirectional promoters have general functional implications in gene regulation is currently unknown [11]

Methods

Results

Discussion

Conclusion