Transcriptional regulation of meiosis in budding yeast

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7. The role of premeiotic DNA replication and/or recombination in controlling EMG expression. Hydroxyurea (HU) is routinely used to inhibit DNA synthesis as it inhibits ribonucleotide reductase (Elford, 1968; Slater, 1973). Shifting cells to meiotic conditions in the presence of 40 mM and 200 mM hydroxyurea leads to a reduction or no expression, respectively, of EMG (Davis et al., 2001; Lamb and Mitchell, 2001). It was suggested that perturbation of premeiotic DNA replication inhibits the transcription of EMG. However, cells deleted for CLB5 along with CLB6 or MUM2/SPOT8 arrest prior to premeiotic DNA replication, with complete expression of EMG (Davis et al., 2001; Dirick et al., 1998; Stuart and Wittenberg, 1998). These results imply that HU blocks DNA replication at different point than clb5 clb6 and mum2, and that only the HU block transmits a checkpoint signal to repress transcription. However, it is also possible, that the effect of HU is not mediated through DNA replication. The latter hypothesis is strengthened by the observation that treatment of yeast cells with HU leads to a substantial decrease in RNA and protein synthesis (Slater, 1973). The effect of HU is mediated through Rpd3 and Sin3 whose presence is required for the reduction in transcription (Lamb and Mitchell, 2001). In addition, in the presence of HU there is a reduction in phosphorylation of Ume6, a phenomenon that is associated with reduction in the activity of Ume6 (Lamb and Mitchell, 2001). 8. The choice between silencing and expression of EMG. Silencing and expression of EMG are dependent on the URS1 element present in their promoter. URS1 serves as a silencing element in vegetative growth media with glucose as the sole carbon source, and is converted into an activation element under meiotic conditions, i.e. nitrogen depletion in the presence of acetate. Fig. 11 summarizes the current knowledge and model for how this regulation is accomplished. Under all growth conditions Ume6 binds to URS1. However, nutrients control the protein complexes that are recruited by Ume6 to the URS1 element. In glucose growth media Ume6 recruits two repression complexes, the HDAC Sin3/Rpd3 that leads to deacetylation of lysines in histone H4, and the Isw2 complex that leads to chromatin remodeling. These two activities are required for complete silencing of EMG. The Sin3/Rpd3 complex is conserved, and functions as a transcriptional silencer in all eukaryotes (Ng and Bird, 2000; Pazin and Kadonaga, 1997). However, Ume6 is not conserved, and in mammals, it is the Mad/Max and nuclear receptors that recruit Sin3/Rpd3 to the DNA (Ng and Bird, 2000; Pazin and Kadonaga, 1997). Similarly, the Isw2 complex is also conserved and functional in all eukaryotes [for review see (Cairns, 1998)]. Under meiotic conditions (acetate media and nitrogen depletion) the Sin3/Rpd3 and Isw2 repression complexes are not functional. Relief of repression of Sin3 depends on Ime1 that is 29
expressed only in the absence of glucose. The mode by which Ime1 relieves repression of Sin3/Rpd3 and how Isw2 does not repress transcription under these conditions are not known. Relief of repression does not suffice for transcriptional activation, and requires Gcn5, the histone acetylase, as well as a transcriptional activation protein, Ime1. Ume6 recruits Ime1 to URS1, and the interaction between these two proteins depends on the absence of glucose and nitrogen. These nutrient signals are transmitted to both Ime1 and Ume6, by two protein kinases, Rim15 and Rim11. Since Rim15 is required for complete phosphorylation of Ume6 in SA and SPM, and since its kinase activity is inhibited in the presence of glucose by PKA, it is assumed that the glucose signal that inhibits the association of Ime1 with Ume6 is transmitted, at least partially, through Rim15. Since Rim15 is only partially required for the interaction of Ime1 with Ume6, the glucose signal must be transmitted through an additional protein. Rim11 phosphorylates both Ime1 and Ume6, and this phosphorylation is essential for their interaction. It is not known how nutrients regulate the function of Rim11. V. Transcriptional regulation of middle meiosis-specific genes (MMG). The regulated transcription of middle meiosis-specific genes (MMG) depends on the presence of two positive elements, MSE (Middle Sporulation Element) (gNCRCAAAA/T) and an Abf1 binding site (Chu et al., 1998; Chu and Herskowitz, 1998; Hepworth et al., 1995; Hepworth et al., 1998; Ozsarac et al., 1995; Ozsarac et al., 1997; Pierce et al., 1998). The MSE elements present in different MMG are not identical, some, for example that in CLB1, function only as positive elements, whereas others, for example that of SMK1 or NDT80 (designated inhere as MSE*), function also as repression elements in vegetative growth conditions and early meiotic times (Pierce et al., 1998; Xie et al., 1999). Schematic illustration on the regulation of MMG is illustrated in Fig. 13, and discussed in the text below. A. Positive regulators of MMG. Ndt80 and Ime2 are two meiosis-specific positive regulators absolutely required for the transcription of MMG (Chu et al., 1998; Chu and Herskowitz, 1998; Hepworth et al., 1998; Ozsarac et al., 1997). The sequential transcription of MMG following transcription of the early genes is due to the regulated transcription of both NDT80 and IME2 (Chu and Herskowitz, 1998; Hepworth et al., 1998). 30
Page 1 and 2: Transcriptional regulation of meios
Page 3 and 4: 3. Proteins required for the associ
Page 5 and 6: I. Introduction The budding yeast S
Page 7 and 8: et al., 2000). On the other hand, i
Page 9 and 10: the UCS4 element upstream of the CY
Page 11 and 12: egulator of Cyr1, CDC25 encodes the
Page 13 and 14: 1998). Furthermore, unlike IREu, IR
Page 15 and 16: In the absence of glucose Sok2 does
Page 17 and 18: autophosphorylation, including on a
Page 19 and 20: hours in SPM, followed by a decline
Page 21 and 22: 4. The SIN3, UME6, and RPD3 genes.
Page 23 and 24: 1993). Nevertheless, when Ime1 is t
Page 25 and 26: However, direct demonstration of ph
Page 27 and 28: 3. Proteins required for the associ
Page 29: heterologous promoter does not supp
Page 33 and 34: structure of hCDK2 reveals that cyc
Page 35 and 36: terminal non-essential domain (Komi
Page 37 and 38: is dependent on Ime2, but in cells
Page 39 and 40: VI. Transcriptional regulation of l
Page 41 and 42: The transcriptional activator that
Page 43 and 44: Functional interaction between Ime1
Page 45 and 46: Bowdish, K. S., and Mitchell, A. P.
Page 47 and 48: Foiani, M., Nadjar-Boger, E., Capon
Page 49 and 50: Jeffrey, P. D., Russo, A. A., Polya
Page 51 and 52: Lindgren, A., Bungard, D., Pierce,
Page 53 and 54: Pazin, M. J., and Kadonaga, J. T. (
Page 55 and 56: Shenhar, G. (2001). TRANSCRIPTIONAL
Page 57 and 58: Szent-Gyorgyi, C. (1995). A biparti
Page 59 and 60: Yoshida, M., Kawaguchi, H., Sakata,
Page 61 and 62: Fig. 4. The function of positive an
Page 63 and 64: Fig. 9. A schematic structure of IM
Page 65 and 66: activation by Ime2 is due to phosph
Page 67 and 68: MCK1 Protein kinase required for ef
Page 69: UME3 A cyclin C homolog that associ

Transcriptional regulation of meiosis in budding yeast

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