Divergent transcription is associated with promoters of transcriptional regulators.

Cyrille Lepoivre (1) , Mohamed Belhocine (1) , Aurélie Bergon (1, 2) , Aurélien Griffon (1) , Miriam Yammine (1) , Laurent Vanhille (1, 3) , Joaquin Zacarias-Cabeza (3) , Marc-Antoine Garibal (1) , Frederic Koch (3) , Muhammad Ahmad Maqbool (3) , Romain Fenouil (3) , Beatrice Loriod (2, 1, 4) , Hélène Holota (1, 2) , Marta Gut (5) , Ivo Gut (5) , Jean Imbert (1, 2) , Jean-Christophe Andrau (3) , Denis Puthier (1, 6) , Salvatore Spicuglia (1)

1 TAGC - Technologies avancées pour le génôme et la clinique
2 CPT - Centre de Physique Théorique - UMR 7332
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 TGML - Transcriptomics and Genomics of Marseille-Luminy
5 Centre Nacional D'Anàlisi Genómica
6 AMU POLYTECH - Polytech Marseille

BACKGROUND: Divergent 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. RESULTS: We 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. CONCLUSIONS: We 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.

Mots clés: Divergent transcription; lncRNA; Bidirectional promoter; GC skew; Developmental transcription factor

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Bio-informatique [q-bio.QM]; Bio-Informatique, Biologie Systémique [q-bio.QM]

Cyrille Lepoivre, Mohamed Belhocine, Aurélie Bergon, Aurélien Griffon, Miriam Yammine, et al.. Divergent transcription is associated with promoters of transcriptional regulators.. BMC Genomics, 2013, 14 (1), pp.914. ⟨10.1186/1471-2164-14-914⟩. ⟨inserm-00924629⟩