Computational Regulatory Genomics

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• Human Promoters Are Intrinsically Directional

Human Promoters Are Intrinsically Directional

S. Duttke,  Scott Allen Lacadie,  Mahmoud Ibrahim,  C. Glass,  D. Corcoran,  C. Benner,  S. Heinz,  J. Kadonaga,  Uwe Ohler 
Molecular Cell 2015 DOI   PubMed  

Abstract

Summary 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.

Additional info

Data:

GRO-Seq and 5'GRO-Seq for HeLa-S3 cell line: GSE63872

 

Processed Results:

Chromatin state segmentation for HeLa-S3 cell line, based on ENCODE ChIP-Seq data: Download