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Vol. 12, Issue 3, 458-461, March 2002

METHODS
Computational Detection and Location of Transcription Start Sites in Mammalian Genomic DNA

Thomas A. Down,1 and Tim J. P. Hubbard

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom

Transcription, the process whereby RNA copies are made from sections of the DNA genome, is directed by promoter regions. These define the transcription start site, and also the set of cellular conditions under which the promoter is active. At least in more complex species, it appears to be common for genes to have several different transcription start sites, which may be active under different conditions. Eukaryotic promoters are complex and fairly diffuse structures, which have proven hard to detect in silico. We show that a novel hybrid machine-learning method is able to build useful models of promoters for >50% of human transcription start sites. We estimate specificity to be >70%, and demonstrate good positional accuracy. Based on the structure of our learned models, we conclude that a signal resembling the well known TATA box, together with flanking regions of C-G enrichment, are the most important sequence-based signals marking sites of transcriptional initiation at a large class of typical promoters.

1 Corresponding author.

12:458-461 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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