Oberbeckmann et al. (Korber lab) – Absolute nucleosome occupancy map for the yeast genome

Absolute nucleosome occupancy map for the Saccharomyces cerevisiae genome

Elisa Oberbeckmann, Michael Wolff, Nils Krietenstein, Mark Heron, Jessica L. Ellins, Andrea Schmid, Stefan Krebs,Helmut Blum, Ulrich Gerland, and Philipp Korber

Genome Res. (2019) 29(12):1996-2009. doi: 10.1101/gr.253419.119. Epub 2019 Nov 6. PMID:31694866

(Elisa Oberbeckmann is a doctoral researcher – and IRTG member –  in Philipp Korber's lab)

This paper reports the first high-resolution map of absolute nucleosome occupancy for any genome. Absolute nucleosome occupancy has been a missing quantity in genome-wide chromatin biology ever since nucleosomes have been mapped for whole genomes. Until now  the peak positions, not the peak heights, were detected. The authors provided the peak heights and found that, at least for yeast, most nucleosomes are present in on avg. 90% of the cells in a cell population, i.e., absolute nucleosome occupancy is very high.

Abstract cited directly from the publication:

Mapping of nucleosomes, the basic DNA packaging unit in eukaryotes, is fundamental for understanding genome regulation because nucleosomes modulate DNA access by their positioning along the genome. A cell-population nucleosome map requires two observables: nucleosome positions along the DNA (“Where?”) and nucleosome occupancies across the population (“In how many cells?”). All available genome-wide nucleosome mapping techniques are yield methods because they score either nucleosomal (e.g., MNase-seq, chemical cleavage-seq) or nonnucleosomal (e.g., ATAC-seq) DNA but lose track of the total DNA population for each genomic region. Therefore, they only provide nucleosome positions and maybe compare relative occupancies between positions, but cannot measure absolute nucleosome occupancy, which is the fraction of all DNA molecules occupied at a given position and time by a nucleosome. Here, we established two orthogonal and thereby cross-validating approaches to measure absolute nucleosome occupancy across the Saccharomyces cerevisiae genome via restriction enzymes and DNA methyltransferases. The resulting high-resolution (9-bp) map shows uniform absolute occupancies. Most nucleosome positions are occupied in most cells: 97% of all nucleosomes called by chemical cleavage-seq have a mean absolute occupancy of 90 ± 6% (±SD). Depending on nucleosome position calling procedures, there are 57,000 to 60,000 nucleosomes per yeast cell. The few low absolute occupancy nucleosomes do not correlate with highly transcribed gene bodies, but correlate with increased presence of the nucleosome-evicting chromatin structure remodeling (RSC) complex, and are enriched upstream of highly transcribed or regulated genes. Our work provides a quantitative method and reference frame in absolute terms for future chromatin studies.