A perspective of promoter architecture from the CCAAT box.
The CCAAT box is an important promoter element regulated by NF-Y, a conserved trimer with histone-like features. We describe a new Position Specific Frequency Matrix (PSFM): we derived from 328 NF-Y promoters from the literature the p-CCAAT, and refined it by analysing ChIP on chip data (g-CCAAT). Interestingly, g-CCAAT has distinct features, such as variations within the CCAAT pentanucleotide. We validated the NF-Y-dependency of several promoters with functional assays. We examined the presence of these PSFMs in all human promoters and detail a number of parameters of CCAAT boxes: position, orientation, distance from TSS, presence of TATA, CpG islands and enrichments of nearby TF elements. The CCAAT genes fall into different GO categories, with cell cycle and chromatin/transcription specifically enriched. Additional findings surfaced: (1) the CCAAT-TATA combination, often mentioned in textbooks, is an exception, rather than the rule. CCAAT promoters are less precise in terms of TSS; (2) There is a good correlation between CCAAT and CpG islands; (3) selective TFs sites are enriched in CCAAT promoters, with precise stereoalignements of some of them. In conclusion, the new features of the CCAAT box and the link with the neighbouring elements will help in the functional classification of promoters.
Dolfini
Diletta
D
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milano, Italy.
Zambelli
Federico
F
Pavesi
Giulio
G
Mantovani
Roberto
R
D001483:Base Sequence / Q000235:genetics*; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004742:Enhancer Elements, Genetic; D006801:Humans; D008967:Molecular Biology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D056510:Position-Specific Scoring Matrices; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D017422:Sequence Analysis, DNA; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins