Divergent Transcription from Active Promoters

TLDR

Transcription initiation by RNA polymerase II is generally considered unidirectional from most genes. The study presents evidence of widespread divergent transcription at protein‑encoding gene promoters. TSSa‑RNAs, 20–90 nt long, flank active promoters with sense peaks 50 nt downstream and antisense peaks 250 nt upstream, co‑localize with RNAPII and H3K4me3 at both sites while H3K79me2 appears only downstream, indicating that short‑distance divergent transcription is common and may keep promoters poised for regulation.

Abstract

Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site-associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisense and sense short RNAs at 250 nucleotides upstream and 50 nucleotides downstream of TSSs, respectively. Northern analysis shows that TSSa-RNAs are subsets of an RNA population 20 to 90 nucleotides in length. Promoter-associated RNAPII and H3K4-trimethylated histones, transcription initiation hallmarks, colocalize at sense and antisense TSSa-RNA positions; however, H3K79-dimethylated histones, characteristic of elongating RNAPII, are only present downstream of TSSs. These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation.