Epimutation of repeated genes in Ascobolus immersus.

Abstract

Ascobolus immersus artificial gene repeats were shown previously to be subject premeiotically to both cytosine methylation and inactivation. We studied sexual progenies of strains harbouring two wild type copies of the endogenous met2 gene lying either in tandem array or at ectopic unlinked positions, by (i) investigating the methylation status, (ii) searching for mutations and (iii) analysing the inheritance of inactivation both in mitotic and sexual offspring. 100% of the ‘tandem’ progeny and 64% of the ‘ectopic’ progeny had methylated repeats and displayed gene inactivation. Similar methylation patterns involving all or most of the cytosine residues within the repeats were observed in both arrangements. The inactivated met2 copies were totally devoid of mutation, as deduced from: (i) extensive restriction site analysis and DNA sequencing; (ii) the finding that all the Met‐ derivatives tested reverted to prototrophy in selective conditions; and (iii) the finding that an inactivated copy of met2 stripped of its methylation through amplification in Escherichia coli regained activity when reintroduced in A.immersus. In the absence of selection, gene silencing and methylation were faithfully maintained through mitotic divisions and through five successive sexual cycles. Altogether, these data show the epimutational nature of this methylation induced premeiotically (MIP) process.

Sensing of DNA non‐homology lowers the initiation of meiotic recomination in yeast

“…The present results can be related to the observation in higher eucaryotes of somatic pairing (Maguire 1967), or RIP and MIP gene inactivation processes in Neurospora (Selker 1990) and Ascobolus (Rhounim et al 1992), respectively. A genome-wide DNA/DNA homology search mechanism involving paranemic interactions has been suggested for all these phenomena (Rossignol & Faugeron 1994;Kleckner & Weiner 1993).…”

Epigenetic inheritance in evolution

“…For the marks on transgenes, and transposable elements, the rate of change is very variable and dependent on environmental and developmental conditions (Mittelsten Scheid, 1995;Jorgensen, 1995). In some cases it has been found that once a transgene or a repeated gene has become repressed by heavy methylation, it is very difficult to re-activate it (Hadchouel et al, 1987;Allen et al, 1990;Rhounim et al, 1992). Often the extent of trans-generational stability of epigenetic marks is unknown, because it has been followed for only a limited number of generations: the induced dwarfism and lowered level of methylation found by Sano et al (1990) in rice was stable for the three generations it was studied, and the induced changes in the phenotype and level of methylation in Triticale were stable for three generations (Heslop-Harrison, 1990); the changed Y chromosome that affected variegation in Drosophila was examined and was stable for 11 generations (Dorn et al, 1993).…”

Transgene‐mediated suppression of chalcone synthase expression in Petunia hybrida results from an increase in RNA turnover

“…Based on data from MIP in Ascobolus (Rhounim et aL, 1992) and RIP in Neurospora (Selker, 1991), it has been hypothesized that the initial event that ultimately leads to suppression might be an interaction between homologous DNA loci (reviewed by Jorgensen, 1992Jorgensen, , 1993Matzke and Matzke, 1993). This then would promote DNA methylation and promoter inactivation.…”