Abstract
Controlling chromatin state constitutes a major regulatory step in gene expression regulation across eukaryotes. While global cellular features or processes are naturally impacted by chromatin state alterations, little is known about how chromatin regulatory genes interact in networks to dictate downstream phenotypes. Using the activity of the canonical galactose network in yeast as a model, here, we measured the impact of the disruption of key chromatin regulatory genes on downstream gene expression, genetic noise and fitness. Using Trichostatin A and nicotinamide, we characterized how drug-based modulation of global histone deacetylase activity affected these phenotypes. Performing epistasis analysis, we discovered phenotype-specific genetic interaction networks of chromatin regulators. Our work provides comprehensive insights into how the galactose network activity is affected by protein interaction networks formed by chromatin regulators.
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Acknowledgements
We thank M. Aldea for comments on the manuscript, the Acar Lab members for helpful discussions, and K. Nelson for cytometry technical assistance. MA acknowledges funding from the National Institutes of Health (R01GM127870 and U54CA209992). The funding bodies did not play any roles in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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DFM and MA designed the experiments and analyses, interpreted the data and results and designed and prepared the manuscript. DFM constructed the strains, performed the experiments and collected the data. MA conceived and supervised the project.
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Moreno, D.F., Acar, M. Chromatin regulatory genes differentially interact in networks to facilitate distinct GAL1 activity and noise profiles. Curr Genet 67, 267–281 (2021). https://doi.org/10.1007/s00294-020-01124-5
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DOI: https://doi.org/10.1007/s00294-020-01124-5