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 that are preferentially used in hippocampus This is the most comprehensive promoter data set for any tissue to date. Using these 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.