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Transcriptional regulation of meiosis in budding yeast

Transcriptional regulation of meiosis in budding yeast

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media and nitrogen depletion) phosphorylation <strong>of</strong> Ime1and Ume6 by Rim11 and Rim15 promotes<br />

the <strong>in</strong>teraction <strong>of</strong> Ime1 with Ume6. Ime1 function is required to relieve repression by S<strong>in</strong>3 and to<br />

activate transcription. In addition, transcriptional activation depends on histone acetylation by<br />

Gcn5.<br />

Fig. 12. Ime2 is highly homologous to hCDK2.<br />

A. Sequence alignment <strong>of</strong> Ime2 to hCDK2. B, Ribbon depiction <strong>of</strong> the crystal structure <strong>of</strong><br />

hCDK2 (Prote<strong>in</strong> Data Bank structure code 1HCL). C. Ribbon depiction <strong>of</strong> the homology based<br />

model <strong>of</strong> Ime2 based on the CDK structure. The follow<strong>in</strong>g stretches <strong>of</strong> residues are colored for<br />

clarity: the ATP b<strong>in</strong>d<strong>in</strong>g site (yellow), The PSTAIRE site (orange), the Catalytic site (red) and the<br />

T-loop (blue). The Ime2 model was prepared us<strong>in</strong>g the 3D-PSSM model<strong>in</strong>g algorithm (Kelley et<br />

al., 2000). The figures were prepared us<strong>in</strong>g InsightII (Accelrys).<br />

Fig. 13. <strong>Transcriptional</strong> <strong>regulation</strong> <strong>of</strong> middle <strong>meiosis</strong>-specific genes.<br />

Ndt80 is the transcriptional activator b<strong>in</strong>d<strong>in</strong>g to the MSE element present <strong>in</strong> the 5’ region <strong>of</strong> all<br />

middle <strong>meiosis</strong>-specific genes (MMG). A subset <strong>of</strong> MMG carries an MSE* site (SMK1 <strong>in</strong><br />

comparison to CLB1) that can be bound by Sum1. Sum1 associates with Hst1 that functions as<br />

histone deacetylase, thus lead<strong>in</strong>g to silenc<strong>in</strong>g under vegetative growth conditions and at early<br />

meiotic times. Under meiotic conditions relief <strong>of</strong> repression is due to degradation <strong>of</strong> Sum1 by<br />

Ime2. Sum1 also represses the transcription <strong>of</strong> NDT80, s<strong>in</strong>ce it carries both an MSE and MSE*<br />

elements. In addition, NDT80 carries two URS1 elements that are bound by Ume6. In vegetative<br />

growth media Ume6 recruits the S<strong>in</strong>3/Rpd3 histone deacetylase complex that represses<br />

transcription. Under meiotic conditions Ume6 recruits Ime1 that can activate transcription, but<br />

only <strong>in</strong> the absence <strong>of</strong> Sum1. Ime2 phosphorylates Ndt80, and this phosphorylation may<br />

contribute to the complete transcriptional activity <strong>of</strong> Ndt80. In the absence <strong>of</strong> meiotic<br />

recomb<strong>in</strong>ation the pachytene checkpo<strong>in</strong>t <strong>in</strong>hibits degradation <strong>of</strong> Sum1 and phosphorylation <strong>of</strong><br />

Ndt80. Consequently, the level <strong>of</strong> Ndt80 is reduced, and the unphosphorylated Ndt80 is impaired<br />

<strong>in</strong> activat<strong>in</strong>g the transcription <strong>of</strong> MMG.<br />

Fig. 14. Positive and negative feedback loops control <strong>meiosis</strong>.<br />

Ime1 shows positive auto<strong>regulation</strong> that is required to relieve repression mediated by Sok2 and<br />

thus for its high-level transcription. Expression <strong>of</strong> early <strong>meiosis</strong>-specific genes (EMG) requires<br />

relief <strong>of</strong> repression <strong>of</strong> S<strong>in</strong>3 and transcriptional activation, two functions that are promoted by<br />

Ime1. The transcription <strong>of</strong> middle genes (MMG) depends on Ime2 and Ndt80. <strong>Transcriptional</strong><br />

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