title: Human promoters are intrinsically directional.
abstract: Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in HeLa cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that about half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process but rather the consequence of the presence of both forward- and reverse-directed core promoters.
authors: Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Sascha H C
authors: SHC
authors: Duttke
authors: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
authors: Scott A
authors: SA
authors: Lacadie
authors: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; Department of Biology, Humboldt University, 10115 Berlin, Germany.
authors: Mahmoud M
authors: MM
authors: Ibrahim
authors: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Christopher K
authors: CK
authors: Glass
authors: Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.
authors: David L
authors: DL
authors: Corcoran
authors: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors: Christopher
authors: C
authors: Benner
authors: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors: Sven
authors: S
authors: Heinz
authors: Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jkadonaga@ucsd.edu.
authors: James T
authors: JT
authors: Kadonaga
authors: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; Department of Biology, Humboldt University, 10115 Berlin, Germany. Electronic address: uwe.ohler@mdc-berlin.de.
authors: Uwe
authors: U
authors: Ohler
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000502:physiology*; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D012319:RNA Polymerase II
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