Coordination between cell size and chromatin structure

Abstract

Cells change size during the cell cycle and in response to external conditions. In order to maintain biomolecule concentrations, gene expression is coordinated with cell size in a process called “scaling”. In fission yeast, scaling has been found to be associated with a genome-wide increase in transcription initiation rates and RNA polymerase II occupancy. However, the mechanistic details that underpin this global increase in transcription have not been defined yet. Since transcription initiation operates in the context of chromatin, we hypothesize that global transcriptional scaling is in part regulated by changes in chromatin state that reflect cell-size increase. To test this hypothesis, we used an analogue sensitive strain of the cyclin-dependent protein kinase Cdc2 (cdc2-asM17). Upon analogue treatment this strain exits the cell cycle in G2 and grows up to a size 3-4 times larger than wild-type after 6h of treatment. By mapping nucleosome occupancy in arrested cdc2-asM17 cells of increasing size, I uncover the link between cell size and the global chromatin architecture. More precisely, I show that cell size increase is accompanied by an increasing occupancy at promoters. These factors occupying the promoter in large cells are MNase-sensitive factors, suggesting that they are not canonical nucleosomes. Moreover, I report that a marker of transcription initiation, H3K9ac, scales with cell size, suggesting a possible role of this post-translational modification in setting a favorable context for an increasing occupancy at promoter of larger cells. Finally, comparing the genome wide distribution of H3 between normal and large cells reveals that for most genes, the protein complex occupying the promoter of large cells is not composed of H3, suggesting that they are not nucleosomal particles, although some promoters indeed present an enrichment of H3 upon cell size increase. Altogether, this work provides insights into the mechanism that regulates scaling.