Genome wide study of NF-Y type CCAAT boxes in unidirectional and bidirectional promoters in human and mouse

Abstract

International audienceA subset of CCAAT boxes are known binding sites for the transcription factor NF-Y. We characterize their number, mismatches to the consensus sequence, and locations in bidirectional and unidirectional promoter sequences in human and mouse. We confront the findings with an analytical null model of DNA sequences and find that NF-Y type CCAAT boxes play key, but distinct roles in the two types of promoters. They are found above chance in both, but in unidirectional only when having few mismatches. In bidirectional, the relative positions of multiple boxes differ from what is expected by chance, suggesting the need for contiguity. In agreement, when there are four boxes (four-box configurations), these have much lower number of mismatches than expected in bidirectional promoters alone. Positioning of the first box differs in the two types of promoters and the null model, and mismatches and positioning are found to be correlated. Finally, four-box configurations are conserved between human and mouse, supporting the relevance of the findings. We conclude that bidirectional and unidirectional promoters, while sharing some similarities, appear to possess distinct regulatory mechanisms at the sequence level

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

“…Thereafter, the importance and widespread distribution of the Y/CCAAT box, as precisely defined by the initial genetic and biochemical experiments, has been substantiated by unbiased genomic studies. The exact sequence and frequency of Y/CCAAT in promoters was assessed using different bioinformatic tools: several labs reported the identification of Y/CCAAT as over-represented in human promoters and enhancers by searching with available matrices, [12][13][14][15][16][17][18][19] and two studies searching for unbiased 'words' enriched within promoters identified Y/CCAAT and precise flanking motifs. 20,21 Y/CCAAT is Enriched in Promoters of 'Cancer' Genes Analysis of transcriptome profiles during cellular transformation identified the Y/CCAAT box as over-represented in promoters of genes overexpressed in diverse types of cancers, breast, colon, thyroid, prostate and leukemias.…”

Spatiotemporal clustering of the epigenome reveals rules of dynamic gene regulation

“…Spatiotemporal epigenomic clusters are predictive of transposons, bidirectional promoters, microRNA promoters, and PIWI RNAs Not only did the spatiotemporal epigenomic clusters predict usual genomic features such as enhancers, promoters, and gene bodies, unexpectedly these clusters were also capable of predicting genomic features, including repeats, bidirectional promoters (Lin et al 2007;Hakkinen et al 2011), microRNA (miRNA) promoters (Marson et al 2008), and PIWI RNAs (piRNAs) (Thomson and Lin 2009). …”

The dual lives of bidirectional promoters

“…The public availability of data from genome wide analyses of factor interactions with chromatin binding by ChIP-chip and ChIP-seq experiments through the ENCODE Project Consortium allows extensive validation of computational analyses of potential and putative factor binding sites enriched in bidirectional promoters across the genome [2,11,16,23]. Through a combination of computational analysis with meta-analysis of ChIP-chip experiments, Lin et al identified factor binding sites that were over-represented in bidirectional promoters [23].…”