Open Access Highly Accessed Research article

Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals

Masahiro Uesaka12, Osamu Nishimura13, Yasuhiro Go45, Kinichi Nakashima2, Kiyokazu Agata1 and Takuya Imamura12*

Author Affiliations

1 Department of Biophysics and Global COE Program, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan

2 Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8581, Japan

3 Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan

4 Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506, Japan

5 Present address: Department of Brain Sciences, Center for Novel Science Initiatives, National Institutes of Natural Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, Japan

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BMC Genomics 2014, 15:35  doi:10.1186/1471-2164-15-35

Published: 17 January 2014



The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples.


We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs.


We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.

Bidirectional promoter; Non-coding RNA; CpG island; Directional RNA-Seq; Gene activation