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Summary: Entry into meiosis is a key developmental decision. We show here that meiotic entry in Saccharomyces cerevisiae is controlled by antisense-mediated regulation of IME4, a gene required for initiating meiosis. In MAT a/α diploids the antisense IME4 transcript is repressed by binding of the a1/α2 heterodimer at a conserved site located downstream of the IME4 coding sequence. MAT a/α diploids that produce IME4 antisense transcript have diminished sense transcription and fail to initiate meiosis. Haploids that produce the sense transcript have diminished antisense transcription and manifest several diploid phenotypes. Our data are consistent with transcription interference as a regulatory mechanism at the IME4 locus that determines cell fate. [Copyright &y& Elsevier]