title: Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program.
abstract: Meiosis 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.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Alves-Rodrigues
authors.affiliation: Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Ferreira
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Moldón
authors.affiliation: Cancer Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona 08035, Spain.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Vivancos
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain; Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain. Electronic address: jose.ayte@upf.edu.
authors.forename: José
authors.initials: J
authors.lastname: Ayté
mesh_terms: D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D008540:Meiosis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C080328:Cig2 protein, S pombe; D019926:Cyclin B; D004271:DNA, Fungal; C500536:Fkh2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C489539:mei4 protein, S pombe