title: Breaking an epigenetic chromatin switch: curious features of hysteresis in Saccharomyces cerevisiae telomeric silencing.
abstract: In addition to gene network switches, local epigenetic modifications to DNA and histones play an important role in all-or-none cellular decision-making. Here, we study the dynamical design of a well-characterized epigenetic chromatin switch: the yeast SIR system, in order to understand the origin of the stability of epigenetic states. We study hysteresis in this system by perturbing it with a histone deacetylase inhibitor. We find that SIR silencing has many characteristics of a non-linear bistable system, as observed in conventional genetic switches, which are based on activities of a few promoters affecting each other through the abundance of their gene products. Quite remarkably, our experiments in yeast telomeric silencing show a very distinctive pattern when it comes to the transition from bistability to monostability. In particular, the loss of the stable silenced state, upon increasing the inhibitor concentration, does not seem to show the expected saddle node behavior, instead looking like a supercritical pitchfork bifurcation. In other words, the 'off' state merges with the 'on' state at a threshold concentration leading to a single state, as opposed to the two states remaining distinct up to the threshold and exhibiting a discontinuous jump from the 'off' to the 'on' state. We argue that this is an inevitable consequence of silenced and active regions coexisting with dynamic domain boundaries. The experimental observations in our study therefore have broad implications for the understanding of chromatin silencing in yeast and beyond.
authors.affiliation: BioMaPS Institute, Rutgers University, Piscataway, NJ, United States of America.
authors.forename: Vijayalakshmi H
authors.initials: VH
authors.lastname: Nagaraj
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America.
authors.forename: Swagatam
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Kavli Institute for Theoretical Physics, University of California Santa Barbara, Santa Barbara, CA, United States of America.
authors.forename: Adel
authors.initials: A
authors.lastname: Dayarian
authors.affiliation: BioMaPS Institute, Rutgers University, Piscataway, NJ, United States of America; Department of Physics and Astronomy, Rutgers University, Piscataway, NJ, United States of America.
authors.forename: Anirvan M
authors.initials: AM
authors.lastname: Sengupta
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D008957:Models, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D056565:Sirtuin 2 / Q000235:genetics; D016615:Telomere / Q000235:genetics*
chemical_list: D002843:Chromatin; D029701:Saccharomyces cerevisiae Proteins; D056565:Sirtuin 2