Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through Chemical Mapping

SUMMARY

Nucleosome organization influences gene activity by controlling DNA accessibility to transcription machinery. Here, we develop a chemical biology approach to determine mammalian nucleosome positions genome-wide. We uncovered surprising features of nucleosome organization in mouse embryonic stem cells. In contrast to the prevailing model, we observe that for nearly all mouse genes a class of fragile nucleosomes occupies previously designated nucleosome-depleted regions around transcription start sites and transcription termination sites. We show that nucleosomes occupy DNA targets for a subset of DNA-binding proteins, including CTCF and pluripotency factors. Furthermore, we provide evidence that promoter-proximal nucleosomes, with the +1 nucleosome in particular, contribute to the pausing of RNA polymerase II. Lastly, we find a characteristic preference for nucleosomes at exon-intron junctions. Taken together, we establish an accurate method for defining the nucleosome landscape, and provide a valuable resource for studying nucleosome-mediated gene regulation in mammalian cells.

Graphical abstract

A chemical approach to accurately map nucleosome positions in mouse embryonic stem cells reveals unexpected insights into nucleosome organization in transcriptional start and stop sites as well as in DNA binding regions for CTCF and pluripotency factors.