Taikichiro Mori Memorial
Research Fund Report
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Research Project: |
System-wide model of redox-regulated chromatin dynamics |
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Name: |
Cornelia Amariei |
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Affiliation: |
Institute
for Advanced Biosciences, Graduate school of media and governance, Keio
University |
Research Project Abstract
Histone modifications regulate the fundamental eukaryotic processes of DNA transcription, replication and repair. The growing amount of information on histone modification sites, enzymatic machineries and modification crosstalk reveal an involved and complex mechanism whose logic remains elusive. Numerous studies have shown that these dynamic events are intimately tied into cellular energetics (through ATP) and redox state. To further investigate this aspect, we have used continuously-grown yeast cultures that auto-synchronise their respiratory activity to produce stable oscillatory dynamics. Trancriptome and metabolome data indicate that cellular events are temporally separated into reductive and oxidative processes, that also correlate with gene DNA structure and nucleosome occupancy patterns. Key currency metabolites such as ATP, NAD(P)H, SAM and Acetyl-CoA required for nucleosome repositioning and histone modifications also show strong oscillatory behaviour, putatively regulating chromatin dynamics. Chromatin Immunoprecipitation experiments revealed several histone modification patterns supporting the idea of a nucleosome-mediated feedback on transcription.
Progress 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.
Further confirmation experiments are underway.