Genome-wide analysis of core promoter structures in Schizosaccharomyces pombe with DeepCAGE.
The core promoter, which immediately flanks the transcription start site (TSS), plays a critical role in transcriptional regulation of eukaryotes. Recent studies on higher eukaryotes have revealed an unprecedented complexity of core promoter structures that underscores diverse regulatory mechanisms of gene expression. For unicellular eukaryotes, however, the structures of core promoters have not been investigated in detail. As an important model organism, Schizosaccharomyces pombe still lacks the precise annotation for TSSs, thus hampering the analysis of core promoter structures and their relationship to higher eukaryotes. Here we used a deep sequencing-based approach (DeepCAGE) to generate 16 million uniquely mapped tags, corresponding to 93,736 positions in the S. pombe genome. The high-resolution TSS landscape enabled identification of over 8,000 core promoters, characterization of 4 promoter classes and observation of widespread alternative promoters. The landscape also allowed precise determination of the representative TSSs within core promoters, thus redefining the 5' UTR for 82.8% of S. pombe genes. We further identified the consensus initiator (Inr) sequence--PyPyPuN(A/C)(C/A), the TATA-enriched region (between position -25 and -37) and an Inr immediate downstream motif--CC(T/A)(T/C)(T/C/A)(A/G)CCA(A/T/C), all of which were associated with highly expressed promoters. In conclusion, the detailed analysis of core promoters not only significantly improves the genome annotation of S. pombe, but also reveals that this unicellular eukaryote shares a highly similar organization in the core promoters with higher eukaryotes. These findings lend additional evidence for the power of this model system in delineating complex regulatory processes in multicellular organisms, despite its perceived simplicity.
a State Key Laboratory on Oncogenes and Bio-ID Center; School of Biomedical Engineering; Shanghai Jiao Tong University ; Shanghai , China.
Hua
H
Li
Jingyi
J
Hou
Ling
L
Bai
Chuansheng
C
Hu
Pan
P
Tong
Yani
Y
Kang
Xiaodong
X
Zhao
Zhifeng
Z
Shao
D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D016384:Consensus Sequence; D021901:DNA, Intergenic / Q000235:genetics; D005800:Genes, Fungal; D016681:Genome, Fungal; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics*; D012984:Software; D016385:TATA Box / Q000235:genetics; D024363:Transcription Initiation Site
D020121:5' Untranslated Regions; D021901:DNA, Intergenic; D022661:RNA, Untranslated
5' UTR annotation; CAGE, cap analysis of gene expression; CDS, coding sequence; DP, broad with a single dominant peak; DeepCAGE, deep sequencing-based cap analysis of gene expression; FDR, false discovery rate; GB, generally broad distribution; GO, Gene Ontology; Inr, initiator; LDP, local-distributed peak; LUSP, local-ultra-sharp peak; MP, broad with bi- or multi- peaks; ORF, open reading frame; SP, single dominant peak; TC, tag cluster; TSS profiling; TSS, transcription start site; core promoter structure; fission yeast; sequence motif analysis