Divergent transcription is associated with promoters of transcriptional regulators

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.

High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq

“…Peak-calling was performed using the HOMER tool with default settings (FDR: 0.001; local and input fold enrichment: 4.0).. Processed data for Pol II, MNase and epigenetic modifications H3K4me1, H3K4me3, H3K27ac NATURE COMMUNICATIONS | DOI: 10.1038/ncomms7905 ARTICLE and H3K27me3 in DP thymocytes were downloaded from GEO 25,29,30 . ChIP-seq data were visualized using the Integrated Genome Browser (http://bioviz.org/igb/).…”

Transcription-Dependent Generation of a Specialized Chromatin Structure at the TCRβ Locus

“…Given the above results, we hypothesized that the DJCb regions might be enriched in initiating short transcripts. To explore this possibility, we performed short-RNA-seq experiments from DRag thymocytes and compared them with strand-specific total (ribosomal-depleted) and polyA RNA-seq profiles previously generated (35). As expected, total and polyA RNA-seq signals overlapped with the DJCb regions and were oriented in the sense of defined transcription units (Fig.…”

Rôle des longs ARN non codants dans le développement normal et pathologique

“…Il est à noter que de nombreux gènes de lncRNA intergéniques ont un site d'initiation de la transcription proche de celui d'un gène codant, la transcription se faisant sur le brin opposé (transcription divergente). Nous avons récemment démontré que les gènes associés à ces transcrits divergents codent fréquemment pour des régulateurs transcriptionnels impliqués dans le développement et la différen-ciation cellulaire [7]. Enfin, certains lncRNA chevauchent de petits ARN, tels que des petits ARN nucléaires (snoRNA) [46] ou des miARN, …”

“…En ce sens, nous avons démontré récemment que les couples lncRNA/ARNm transcrits de façon divergente sont le reflet d'un mécanisme spécialisé de la régula-tion transcriptionnelle impliquant des promoteurs bidirectionnels [7].…”