Global roles of Ste11p, cell type, and pheromone in the control of gene expression during early sexual differentiation in fission yeast

Abstract

Fission yeast cells belong to one of two specialized cell types, M or P. Specific environmental conditions trigger sexual differentiation, which leads to an internal program starting with pheromone signaling between M and P cells, followed by mating, meiosis, and sporulation. The initial steps of this process are controlled by Ste11p, a master transcriptional regulator that activates the expression of cell type-specific genes (only expressed in either M or P cells) as well as genes expressed in both M and P cells. Pheromone signaling is activated by Ste11p-dependent transcription and, in turn, enhances some of this transcription in a positive feedback. To obtain a genomewide view of Ste11p target genes, their cell-type specificity, and their dependence on pheromone, we used DNA microarrays along with different genetic and environmental manipulations of fission yeast cells. We identified 78 Ste11p-dependent genes, 12 and 4 of which are only expressed in M and P cells, respectively. These genes show differing grades of pheromone dependencies for Ste11p-activated transcription, ranging from complete independence to complete dependence on pheromone. We systematically deleted all novel cell type-specific genes and characterized their phenotype during sexual differentiation. A comparison with a similar data set from the distantly related budding yeast reveals striking conservation in both number and types of the proteins that define cell types. Given the divergent mechanisms regulating cell type-specific gene expression, our results highlight the plasticity of regulatory circuits, which evolve to allow adaptation to changing environments and lifestyles.expression profiling ͉ master transcriptional regulator ͉ mating type ͉ microarray ͉ Schizosaccharomyces pombe C ellular differentiation is driven to a large extent by specific programs of gene expression. Yeast has distinct cell types that are required for mating, meiosis, and sporulation; this sexual differentiation provides a useful model system to understand the differentiation into specialized cell types in multicellular organisms. How the regulation of gene expression leads to specialized cell types is relatively well understood at a genomewide level in the budding yeast Saccharomyces cerevisiae (1). In this yeast, two haploid cell types, a and ␣, mate with each other at the first opportunity to form diploid a͞␣ cells, which can undergo meiosis and sporulation under appropriate environmental conditions (reviewed in ref.2).Cells of the fission yeast Schizosaccharomyces pombe also come in two specialized cell types, called P (or hϩ) and M (or h-) mating types. Heterothallic strains have a fixed mating type (P or M), whereas homothallic strains (h90) can switch between both types. Unlike budding yeast, however, fission yeast cells will mate only under specific environmental conditions, most notably nitrogen starvation; the resulting diploid cells then immediately undergo meiosis and sporulation (reviewed in refs. 3 and 4). The two distantly related yeasts thus provid...

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination

“…3B), which encodes a chaperone involved in loading of the centromere-specific histone H3 variant, CENP-A (36)(37)(38). Mc likely induces the expression of this locus because a previous study has shown that scm3 is expressed at higher levels in M cells, compared with P cells (35). Surprisingly, we also…”

“…Scm3 is related to mammalian holiday junction-recognizing protein (46) and could potentially act together with Swi2-Swi5 to promote mating-type switching. We also found Mc localizing to map2 and map4, which are expressed specifically in P cells (35,39). Both of these genes possess long 5′ UTRs that contain several M boxes.…”

“…S2). These included genes such as mfm2 and mam1 that are involved in the production and secretion of M factor, respectively (33,34), and mam3, which encodes the M cell-type-specific agglutinin that allows specific aggregation between cells of opposite mating type (35). Interestingly, Mc was found to be enriched at the promoter region of scm3 (Fig.…”

“…Thus, Abp1-dependent or -independent recruitment of Mc to swi2 and swi5, respectively, might stimulate Ste11-dependent expression of these loci. Indeed, Ste11 is required for a subtle increase in swi5 transcript levels in M cells (35). However, considering that the HMG box of SRYrelated proteins resembles RNA-binding domains, and that these factors have roles in RNA metabolism (43,44), it is possible that Mc acts in a similar manner to modulate Swi2 and Swi5 protein levels.…”

“…S2) that express specifically in P cells (35,39), raising the possibility that Mc regulates expression of these loci. These analyses also detected prominent Mc peaks near several loci that show no obvious induction in M cells (Fig.…”