Meiosis is the process that produces haploid gametes from diploid parental cells. Similar to other developmental pathways, many genes required for meiosis and spore formation in the budding yeast Saccharomyces cerevisiae
display a transient transcription profile (7
). During vegetative growth, their mRNA levels are low but increase dramatically at precise stages in meiosis. This expression is usually followed by an equally rapid repression that returns the mRNA to mitotic levels.
The vegetative repression of a group of genes designated “early meiotic genes” (EMG) requires the recruitment of the histone deacetylase (HDAC) Rpd3p (13
) and the chromatin-remodeling factor Isw2p (10
) by the Ume6p DNA binding protein (31
). Ume6p binds an element termed upstream repressor sequence 1 (URS1) that is responsible for the full repression and activation of several early meiotic genes (3
). The Ume6p-Rpd3p association occurs through the global corepressor Sin3p (13
). Similarly, the last known member of this repression complex, Ume1p (30
), associates with Rpd3p in an Sin3p-dependent manner (17
). The function of Ume1p in this complex is currently unknown, but it is suggested to be a tightly associated cofactor (41
The interactions between the URS1 regulatory element and its associating factors are complex. For example, URS1 is also required for the repression of several vegetative genes (22
). Of these loci, only CAR1
is repressed by Ume6p (23
), while Sin3p alone regulates HO
). Given the diverse loci regulated by URS1, it is likely that specificity is introduced through the interaction of additional factors targeted to the various promoters. Indeed, Abf1p helps stimulate transcription of the URS1-regulated meiotic gene HOP1
). Similarly, an element termed the auxiliary repression element (ARE) has been identified genetically that contributes to vegetative repression of the meiosis-specific heat shock gene HSP82
). Therefore, the context in which URS1 is found may allow this single element to respond to different stimuli and function in a positive or negative manner.
Sin3p belongs to a conserved gene family that contains four paired amphipathic helix (PAH) protein-protein interaction domains (see reference 29
for a review). Mutational analysis in yeast revealed that of the four PAH domains, PAH3 is required for the repression of several genes, including HO
, and IME2
). Functionally, PAH3 helps recruit the HDAC complex and other corepressors, while PAH2 mediates the interaction with Ume6p in yeast (44
). The roles of the PAH domains in transcriptional repression appear conserved in the human Sin3 (hSin3). For example, hSin3p also associates with the histone deacetylase HDAC1 (15
), while PAH2 binds transcription factors (2
). Less is known about the other two PAH domains. PAH1 recruits a variety of corepressors, depending on the gene context (29
), while PAH4 is reported to bind the enzyme O
-acetylglucosamine transferase (OGT) to help repress transcription in higher eukaryotes (45
). These results indicate that the PAH domains perform separate, but complementary, roles in mediating transcriptional repression.
Although it regulates diverse gene sets, mutants lacking SIN3
do not display significant growth defects (39
). However, Sin3p is required for the execution of the first meiotic nuclear division (30
), with mutants arresting in meiotic prophase I (11
). This present study explores the role of Sin3p in controlling meiotic gene expression. We find evidence for two separate Sin3p-dependent regulatory systems, one repressing EMG transcription during mitotic cell division, and the other functioning to reestablish repression as the cells complete meiosis.