Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program

• Mei4 binds a subset of Fkh2-regulated genes only during meiosis
• Fkh2 marks promoters for Mei4 binding during meiosis
• Fkh2 phosphorylation by CDK diminishes its affinity for DNA
• Mei4 and Fkh2 do not coexist on the same promoters

SummaryMeiosis is a differentiated program of the cell cycle that is characterized by high levels of recombination followed by two nuclear divisions. In fission yeast, the genetic program during meiosis is regulated at multiple levels, including transcription, mRNA stabilization, and splicing. Mei4 is a forkhead transcription factor that controls the expression of mid-meiotic genes. Here, we describe that Fkh2, another forkhead transcription factor that is essential for mitotic cell-cycle progression, also plays a pivotal role in the control of meiosis. Fkh2 binding preexists in most Mei4-dependent genes, inhibiting their expression. During meiosis, Fkh2 is phosphorylated in a CDK/Cig2-dependent manner, decreasing its affinity for DNA, which creates a window of opportunity for Mei4 binding to its target genes. We propose that Fkh2 serves as a placeholder until the later appearance of Mei4 with a higher affinity for DNA that induces the expression of a subset of meiotic genes.

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