A whole genome analysis of 5′ regulatory regions of human genes for putative cis-acting modulators of nucleosome positioning

We have carried out in silico analysis of upstream regions of 23,034 genes from the human genome for sequence motifs, which can potentially affect nucleosome positioning. Nucleosome exclusion elements (NEE) occur in 12% of the genes while less than 1% contain nucleosome positioning elements (NPE). NEE are significantly higher in 5′ regions of certain categories of genes, namely, genes with active promoters, genes localised to gene-rich chromosomes 16, 17 and 19, genes having significantly higher expression levels and higher levels of occupancy of general transcription machinery proteins. NEE are also enriched in housekeeping and TATA-less genes, but are significantly under-represented in the upstream region of genes functionally classified under ‘organ development’ and ‘morphogenesis’ categories. Further, DNase I hypersensitive sites which co-localise with NEE, preferentially occur in 5′ regulatory regions. Considering the positioning sequences identified so far, we speculate that low affinity nucleosome positioning in the upstream sequences of genes in the human genome is the default state requiring activation through chromatin remodelling, while, there appears to be a selection for nucleosome excluding sequences in the upstream sequences of genes that are ubiquitously expressed.