A novel mechanism of epigenetic regulation: nucleosome-space occupancy.

Nucleosome positioning around the gene space (or transcriptional unit) plays a crucial role for gene regulation but we do not know if the spatial organization--nucleosome-space occupancy or nucleosome density in a defined sequence unit length--contributes to the regulation complexity of mammalian gene expression. Using our own rmRNA-Seq (ribosomal RNA-minus RNA sequencing) and publically available ChIP-Seq (H3) data from mouse stem cells, we discovered a non-random distribution of nucleosomes along chromosomes, and further genome-wide studies on histone modifications, DNA methylation, transcriptional activity, gene density, and base compositional dynamics, demonstrated that nucleosome-space occupancy of genomic regions--clustered genes and their intergenic spaces--show distinctive features, where a high occupancy coincides with active transcription, intensive histone modifications, poor DNA methylation, and higher GC contents as compared to the nucleosome-poor regions. We therefore proposed that nucleosome-space occupancy as a novel mechanism of epigenetic gene regulation, creating a vital environment for transcriptional activation.