Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE

Abstract

Finding and characterizing mRNAs, their transcription start sites (TSS) and their associated promoters is a major focus in post-genome biology. Mammalian cells have at least 5-10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high throughput sequencing of 5' cDNA tags, DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth of novel core promoters which are preferentially used in hippocampus: this is the most comprehensive promoter dataset for any tissue to date. Using this data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.