Transcriptional regulatory network for sexual differentiation in fission yeast.
BACKGROUND
Changes in gene expression are hallmarks of cellular differentiation. Sexual differentiation in fission yeast (Schizosaccharomyces pombe) provides a model system for gene expression programs accompanying and driving cellular specialization. The expression of hundreds of genes is modulated in successive waves during meiosis and sporulation in S. pombe, and several known transcription factors are critical for these processes.


RESULTS
We used DNA microarrays to investigate meiotic gene regulation by examining transcriptomes after genetic perturbations (gene deletion and/or overexpression) of rep1, mei4, atf21 and atf31, which encode known transcription factors controlling sexual differentiation. This analysis reveals target genes at a genome-wide scale and uncovers combinatorial control by Atf21p and Atf31p. We also studied two transcription factors not previously implicated in sexual differentiation whose meiotic induction depended on Mei4p: Rsv2p induces stress-related genes during spore formation, while Rsv1p represses glucose-metabolism genes. Our data further reveal negative feedback interactions: both Rep1p and Mei4p not only activate specific gene expression waves (early and middle genes, respectively) but are also required for repression of genes induced in the previous waves (Ste11p-dependent and early genes, respectively).


CONCLUSIONS
These data give insight into regulatory principles controlling the extensive gene expression program driving sexual differentiation and highlight sophisticated interactions and combinatorial control among transcription factors. Besides triggering simultaneous expression of gene waves, transcription factors also repress genes in the previous wave and induce other factors that in turn regulate a subsequent wave. These dependencies ensure an ordered and timely succession of transcriptional waves during cellular differentiation.
Mata
Juan
J
Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1HH, UK. jm593@cam.ac.uk
Wilbrey
Anna
A
Bähler
Jürg
J
D051696:Activating Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008540:Meiosis / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D012733:Sex Differentiation / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D051696:Activating Transcription Factors; D029702:Schizosaccharomyces pombe Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C102103:atf21 protein, S pombe; C489539:mei4 protein, S pombe; C087051:rep1 protein, S pombe