Chromatin regulatory genes differentially interact in networks to facilitate distinct GAL1 activity and noise profiles
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ORIGINAL ARTICLE
Chromatin regulatory genes differentially interact in networks to facilitate distinct GAL1 activity and noise profiles David F. Moreno1,2 · Murat Acar1,2,3 Received: 9 August 2020 / Revised: 20 October 2020 / Accepted: 22 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 phenotypespecific 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. Keywords GAL network · GAL1 · Chromatin state · Chromatin regulation · Gene expression · Noise · Yeast · TSA · Nicotinamide
Introduction Regulation of chromatin state for initiation and progression of gene expression is a major mechanism for eukaryotic transcriptional control (Wu 1997; Luo and Dean 1999; Li et al. 2007). The nucleosome, composed by a histone octamer and 147 bp of DNA wrapped around them, forms the basic units of the chromatin (Richmond and Davey 2003). Special protein complexes, known as chromatin regulators, can alter chromatin state by chemically modifying histone Communicated by M. Kupiec. Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s00294-020-01124-5) contains supplementary material, which is available to authorized users. * Murat Acar [email protected] 1
Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USA
2
Systems Biology Institute, Yale University, 850 West Campus Drive, West Haven, CT 06516, USA
3
Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA
tails, relocating nucleosomes along the DNA and tuning the histone turnover (Rando and Winston 2012). These actions can be exerted locally or globally; for example, a high level of chromatin condensation is achieved during mitosis (Vas et al. 2007), while only certain gene clusters’ expression are regulated by the state of their chromatin in response to external stress (Shivaswamy and Iyer 2008). The most common chemical modifications to alter chromatin state are acetylation and methylation of the histone tails (Millar and Grunstein 2006; Bannister and Kouzarides 2011). Acetylation keeps the chromatin in a more op
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