Transcriptional initiation of each gene is assumed to be independently controlled in mammals. On the other hand, recent large-scale transcriptome analyses have shown that the genome is pervasively transcribed, such that the most of its DNA gives rise to RNAs1,2,3,4. This raises the question of whether it is possible to pinpoint and activate a particular locus without perturbing numerous neighbouring transcripts. Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulation5 is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs. Even in surrounding intergenic regions, transcriptional activation took place at the same time. Acetylation levels of histone H3 and H4 are elevated along with the IEG induction and neighbouring co-upregulation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway or the transcription factor SRF suppresses all transcriptional upregulation. These results suggest that transcriptional activation has a ripple effect, which may be advantageous for coordinated expression.
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We thank I. Smith for helpful discussion and M. McMahon for ΔB-Raf–ER cells. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to E.N.).
The authors declare no competing financial interests.
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Ebisuya, M., Yamamoto, T., Nakajima, M. et al. Ripples from neighbouring transcription. Nat Cell Biol 10, 1106–1113 (2008). https://doi.org/10.1038/ncb1771
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