title: Divergent transcription is associated with promoters of transcriptional regulators.
abstract: 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.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Lepoivre
authors.forename: Mohamed
authors.initials: M
authors.lastname: Belhocine
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bergon
authors.forename: Aurélien
authors.initials: A
authors.lastname: Griffon
authors.forename: Miriam
authors.initials: M
authors.lastname: Yammine
authors.forename: Laurent
authors.initials: L
authors.lastname: Vanhille
authors.forename: Joaquin
authors.initials: J
authors.lastname: Zacarias-Cabeza
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Garibal
authors.forename: Frederic
authors.initials: F
authors.lastname: Koch
authors.forename: Muhammad Ahmad
authors.initials: MA
authors.lastname: Maqbool
authors.forename: Romain
authors.initials: R
authors.lastname: Fenouil
authors.forename: Beatrice
authors.initials: B
authors.lastname: Loriod
authors.forename: Hélène
authors.initials: H
authors.lastname: Holota
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.affiliation: Technological Advances for Genomics and Clinics (TAGC), Case 928, 163 Avenue de Luminy, 13288, Marseille cedex 09, France. andrau@ciml.univ-mrs.fr.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Andrau
authors.forename: Denis
authors.initials: D
authors.lastname: Puthier
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spicuglia
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D001482:Base Composition; D002843:Chromatin / Q000235:genetics; D018899:CpG Islands; D044127:Epigenesis, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA; D060168:Thymocytes; D014158:Transcription, Genetic
chemical_list: D016375:Antisense Elements (Genetics); D002843:Chromatin; D062085:RNA, Long Noncoding; D012333:RNA, Messenger