Ripples from neighbouring transcription

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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 RNAs. 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 stimulations 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.

Details

Original languageEnglish
Pages (from-to)1106-13
Number of pages8
JournalNature cell biology
Volume10
Issue number9
Publication statusPublished - Sept 2008
Peer-reviewedYes

External IDs

Scopus 51049102332

Keywords

Keywords

  • Acetylation, Animals, DNA, Intergenic/genetics, Gene Expression Regulation, Genes, Immediate-Early, Histones/metabolism, Mice, Mitogen-Activated Protein Kinases/metabolism, NIH 3T3 Cells, Oligonucleotide Array Sequence Analysis, RNA, Messenger/genetics, Saccharomyces cerevisiae/genetics, Serum Response Factor/metabolism, Transcription, Genetic