Chromosomal Inheritance of Epigenetic States in Fission Yeast During Mitosis and Meiosis

Abstract

Inheritance of the active and inactive states of gene expression by individual cells is crucial for development. In fission yeast, mating-type region consists of three loci called mat1, mat2, and mat3. Transcriptionally silent mat2 and mat3 loci are separated by a 15 kb interval, designated the K-region, and serve as donors of information for transcriptionally active mat1 interconversion. In a strain carrying replacement of 7.5 kb of the K-region with the ura4 gene, we discovered that ura4 silencing and efficiency of mating-type switching were covariegated and were regulated by an epigenetic mechanism. Genetic analyses demonstrated that epigenetic states were remarkably stable not only in mitosis but also in meiosis and were linked to the mating-type region. This study indicates that different epigenetic states are heritable forms of chromatin organization at the mat region.

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

“…Unlike yeast, sister cells during asymmetric cell division in higher eukaryotes are often nonrandomly placed with respect to adjoining cells (Horvitz and Herskowitz 1992). Epigenetically mediated states of gene expression can be inherited chromosomally through multiple cell divisions (Grewal and Klar 1996;Thon and Friis 1997), and the opportunity for altering the epigenetic state during DNA replication exists (Zhang et al 2000). Therefore, the possibility for biologically relevant biased segregation of chromatids from both homologs can be imagined.…”

Epigenetic regulation of aging stem cells

“…Changes to chromatin are thought to be reversible and are thus ideally situated to be molecular effectors of stem cell rejuvenation ( Figure 2). The fact that chromatin changes can themselves be mitotically inherited (Grewal and Klar, 1996;Cavalli and Paro, 1998;Martin and Zhang, 2007) raises the possibility that an additional level of regulation in aging stem cells is the heritability of environmentally induced chromatin changes in parent stem cells to daughter cells. This review will focus primarily on changes in histone modifications.…”

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

“…For the latter it ranges 7 from subsecond for enzyme binding/unbinding events, to months or longer for histone memory duration. For example, epigenetic state switches for the above-mentioned S. Pombe mutant take place about every 200 days on average (8,9). Therefore mathematical modeling is necessary to fill in the huge gaps between the experimentally explored molecular events and collective epigenetic dynamics.…”

“…A mutant has been constructed with portion of the silenced region removed and an ura4+ reporter gene inserted. Experimental studies on the mutant revealed that the DNA region (~ 60 nucleosomes) can exist in an inheritable epigenetic active or silent state, with a very low probability of stochastic transition between the two states of about 5 × 10 -4 per cell division (8,9). Furthermore, the two copies of the chromosomal region within one cell can exist in different epigenetic states.…”