| Summary: | Epigenetic switches encode their state information either locally, often via covalent modification of DNA or histones, or
globally, usually in the level of a trans-regulatory factor. Here we examine how the regulation of cis-encoded epigenetic
switches controls the extent of heterogeneity in gene expression, which is ultimately tied to phenotypic diversity in a
population. We show that two copies of the FLO11 locus in Saccharomyces cerevisiae switch between a silenced and
competent promoter state in a random and independent fashion, implying that the molecular event leading to the
transition occurs locally at the promoter, in cis. We further quantify the effect of trans regulators both on the slow
epigenetic transitions between a silenced and competent promoter state and on the fast promoter transitions associated
with conventional regulation of FLO11. We find different classes of regulators affect epigenetic, conventional, or both forms
of regulation. Distributing kinetic control of epigenetic silencing and conventional gene activation offers cells flexibility in
shaping the distribution of gene expression and phenotype within a population.
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