Taikichiro Mori Memorial Research Fund Report



Research Project:

System-wide model of redox-regulated chromatin dynamics


Cornelia Amariei


Institute for Advanced Biosciences, Graduate school of media and governance, Keio University



Research Project Abstract

Previous studies using continuously-grown yeast have shown that the transcriptome can be highly oscillatory, hinting at a, yet to be elucidated, global transcription mechanism. A recent Fourier-based analysis method of oscillating transcriptome datasets identified 7 consensus clusters of gene expression. Further analyses of a large compendium of high-throughput data implicate differential promoter structures and nucleosome occupancy patterns (and the energetic requirements for remodelling) in the regulation of each of these clusters. Subsequent time-series experimental data on the metabolome and nucleosome positioning over several respiratory oscillations further implicates the energetics of the cell feeding back onto global nucleosome remodelling events to differentially regulate gene expression. Taken together our data provides a simplified view of the global transcription regulation mechanism driven by the energetic state of the cells shaping chromatin structure.



We have conducted a series of Chromatin Immunoprecipitation experiments on time-series samples, aimed at better understanding the dynamics of the transcription regulation with regard to histone positioning and modifications. Although the results are still preliminary and further work is needed, they suggest that:
(a) the waves of mRNA quantities shown in previous studies are indeed regulated at transcriptional level;
(b) histone acetylation shows differences over the respiratory cycle and correlates with differentially expressed genes;
(c) nucleosome positioning upstream of transcription start site (TSS) may be a dynamic, global property, strongly linked to the respiratory cycle.
We have further developed a simplified, reliable method for obtaining total nucleosomal DNA and have conducted a 40-timepoint tiling array analysis of the nucleosomal versus total DNA. We are currently processing this data and developing an R package dedicated to analyzing and visualizing nucleosome dynamics on both specific genomic regions and genome-wide changes.


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