Genomic architecture and nucleotide composition of tandem genes Definition of controls Enriched motifs in STIRs Enriched binding of proteins at STIRs Enriched binding of proteins at STIRs Features promoting the proper expression of tandem gene pairs Features promoting the proper expression of tandem gene pairs Pol2 accumulates in STIRs SPT6 degradation is associated with Pol2 paucity at STIRs ChIP-seq signal of histone marks at STIRs NELF-E involvement in transcription regulation of downstream tandem genes Unique features of transcription termination and initiation at closely spaced tandem human genes

Hundreds of human genes are transcribed in close proximity to each other and on the same strand. A systematic computational analysis reveals unique genomic features associated with intergenic regions separating these tandem genes.


The synthesis of RNA polymerase II (Pol2) products, which include messenger RNAs or long noncoding RNAs, culminates in transcription termination. How the transcriptional termination of a gene impacts the activity of promoters found immediately downstream of it, and which can be subject to potential transcriptional interference, remains largely unknown. We examined in an unbiased manner the features of the intergenic regions between pairs of ‘tandem genes’—closely spaced (< 2 kb) human genes found on the same strand. Intergenic regions separating tandem genes are enriched with guanines and are characterized by binding of several proteins, including AGO1 and AGO2 of the RNA interference pathway. Additionally, we found that Pol2 is particularly enriched in this region, and it is lost upon perturbations affecting splicing or transcriptional elongation. Perturbations of genes involved in Pol2 pausing and R loop biology preferentially affect expression of downstream genes in tandem gene pairs. Overall, we find that features associated with Pol2 pausing and accumulation rather than those associated with avoidance of transcriptional interference are the predominant driving force shaping short tandem intergenic regions.


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