Transcriptional activation by bidirectional RNA polymerase II elongation over a silent promoter

Transcriptional interference denotes negative cis effects between promoters. Here, we show that promoters can also interact positively. Bidirectional RNA polymerase II (Pol II) elongation over the silent human endogenous retrovirus (HERV)-K 18 promoter (representative of 2.5 x 10(3) similar promoters genomewide) activates transcription. In tandem constructs, an upstream promoter activates HERV-K 18 transcription. This is abolished by inversion of the upstream promoter, or by insertion of a poly(A) signal between the promoters; transcription is restored by poly(A) signal mutants. TATA-box mutants in the upstream promoter reduce HERV-K 18 transcription. Experiments with the same promoters in a convergent orientation produce similar effects. A small promoter deletion partially restores HERV-K 18 activity, consistent with activation resulting from repressor repulsion by the elongating Pol II. Transcriptional elongation over this class of intragenic promoters will generate co-regulated sense-antisense transcripts, or, alternatively initiating transcripts, thus expanding the diversity and complexity of the human transcriptome.