Genome-wide nucleosome positioning during embryonic stem cell development

Tissue- and disease-specific features of nucleosome positioning have recently been reported. A new study set out to identify features of nucleosome positioning at functional genomic elements during lineage commitment from mouse embryonic stem cells to neural progenitors and embryonic fibroblasts. The results reveal regulatory mechanisms of cell differentiation that involve nucleosome positioning. We determined genome-wide nucleosome occupancies in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell-type- and protein-specific binding preferences of transcription factors to sites with either low (Myc, Klf4 and Zfx) or high (Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome-depleted regions around transcription start and transcription termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to CpG content or histone methylation marks. Throughout the genome, nucleosome occupancy was correlated with certain histone methylation or acetylation modifications. In addition, the average nucleosome repeat length increased during differentiation by 5–7 base pairs, with local variations for specific regions. Our results reveal regulatory mechanisms of cell differentiation that involve nucleosome repositioning.