A Yeast Catabolic Enzyme Controls Transcriptional Memory

Abstract

It has been postulated that chromatin modifications can persist through mitosis and meiosis, thereby securing memory of transcriptional states. Whether these chromatin marks can self-propagate in progeny independently of relevant trans-acting factors is an important question in phenomena related to epigenesis. "Adaptive cellular memory" displayed by yeast cells offers a convenient system to address this question. The yeast GAL genes are slowly activated by Gal4 when cells are first exposed to galactose, but their progeny, grown in glucose media, exhibit a fast activation mode upon re-exposure to this sugar. This "galactose memory" persists for several generations and was recently proposed to involve chromatin modifications and perinuclear topology of the GAL genes cluster. Here, we perform a heterokaryon assay demonstrating that this memory does not have a chromatin basis but is maintained by cytoplasmic factor(s) produced upon previous galactose induction. We show that Gal3, the cytoplasmic rate-limiting factor that releases the Gal4 activator, is dispensable for preserving galactose memory. Instead, the important memory determinant is a close Gal3 homolog, the highly expressed Gal1 galactokinase, the residual activity of which preserves memory in progeny cells by rapidly turning on the Gal4 activator upon cells' re-exposure to galactose.

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…They called the processes and mechanisms that underlie cellular inheritance "epigenetic inheritance systems" (abbreviated to EISs by Maynard Smith [1990]). Cell heredity may occur when an induced gene-product is diluted very slowly by cell divisions, so that its concentration remains above the threshold required for its activity for several cell generations (Zacharioudakis et al 2007), but such "memory" is short-term. For more persistent memory and cell heredity, autocatalysis is necessary, and all the EISs we describe depend on mechanisms that enable self-perpetuation.…”

Structure and Function in the Budding Yeast Nucleus

“…Both GAL1 and INO1 genes are more rapidly reactivated after short-term repression, and this correlates with their persistence at the NPC after the inducing agent was removed. Although mechanisms involving cytoplasmic factors have also been implicated in rapid gene reactivation (Zacharioudakis et al 2007), GAL gene transcriptional memory was nonetheless correlated with the formation of persistent loops between the 59 and 39 ends of the gene and association with the NPC (Laine et al 2009;Tan-Wong et al 2009). In the case of INO1, an 11-bp sequence appears to control both peripheral targeting and H2A.Z incorporation after repression (Brickner et al 2007;Light et al 2010).…”

Cellular Memory of Acquired Stress Resistance inSaccharomyces cerevisiae

“…There are several possible mechanisms of cellular memory in yeast, including propagation of chromatin marks (Brickner 2009;Kundu and Peterson 2009;Kaufman and Rando 2010), inheritance of long-lived memory factors (Acar et al 2005;Zacharioudakis et al 2007;Kundu and Peterson 2010), and feedback in signaling pathways that can maintain a response once cellular memory is activated (Xiong and Ferrell 2003;Acar et al 2005;Mettetal et al 2008). We found no requirement for several chromatin factors implicated in expression memory, including the deacetylase SIR2, the Pho23p subunit of the Rpd3-large histone deacetylase complex, or the histone variant H2A.z (Q. Guan and A. P. Gasch, unpublished data).…”

“…Several studies have demonstrated transcriptional memory in cells previously exposed to galactose or inositol starvation, if cells are re-exposed to the nutrient shifts at a later time (Acar et al 2005;Brickner et al 2007;Kundu et al 2007;Zacharioudakis et al 2007). We therefore measured genomic expression in cells responding over the course of 60 min to a viable dose of 0.5 mM H 2 O 2 .…”