Transcriptional regulation of meiosis in budding yeast

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3. Respiration and the transcription of IME1. The presence of glucose prevents the activity of the mitochondria whose function is required for sporulation (Berger and Yaffe, 2000). The transcription of IME1 is absent in diploid cells without mitochondria – petites, or in cells treated with oligomycin - an inhibitor of the mitochondrial ATPase (Treinin and Simchen, 1993). It is not known whether mitochondrial function is also required at a stage preceding the transcription of IME1. The site within IME1 that responds to mitochondria function is not known, nor is it known how the respiration signal is transmitted. The connection between mitochondria function and IME1 transcription is also evident from the identification of the Rim1 (Rim101) Rim8, Rim9, Rim13 and Rim20 proteins as positive regulators of IME1 (Li and Mitchell, 1997; Su and Mitchell, 1993a). RIM1 encodes a C2H2 zinc finger protein that is required for high-level expression of IME1 as well as for efficient sporulation (Su and Mitchell, 1993b). Activation of Rim1 requires its cleavage by the products of Rim8, Rim9 and Rim13 (Li and Mitchell, 1997), as well as the activity of Rim20 that might be required for presenting Rim1 to Rim13 (Xu and Mitchell, 2001). Rim1 is localized to mitochondria, and is required for mitochondria DNA replication, and consequently for the maintenance of the mitochondria (Berger and Yaffe, 2000; Van Dyck et al., 1992). Thus, the effect of these RIM1,8,9,13,20 genes on the transcription of IME1 may be indirect, through their effect on the maintenance of the mitochondria. D. Additional proteins regulating the transcription of IME1. 1. Mck1. MCK1 encodes a protein kinase required for efficient transcription of IME1, for expression of early and middle genes such as IME2 and SPS1,2 respectively, and for spore maturation (Neigeborn and Mitchell, 1991). Expression of IME1 from the hetrologous GAL1 promoter suppresses the requirement of Mck1 for the transcription of EMG and MMG, but spore maturation remains defective, suggesting that Mck1 directly regulate IME1 transcription and spore maturation (Neigeborn and Mitchell, 1991). MCK1 is one of 4 yeast genes showing homology to mammalian glycogen synthase kinase 3 (GSK3-β), RIM11, YOL128c, and MRK1. These homologs are not required for the transcription of IME1 (Hajji et al., 1999; Mandel et al., 1994; Rabitsch et al., 2001), suggesting that the transcription of IME1 is only partially dependent on Mck1. Mck1 inhibits the kinase activity of PKA both in vitro and in vivo, through a mechanism that does not depend on Mck1 kinase activity (Rayner et al., 2002). This result implies that deletion of MCK1 might increase rather than decrease the transcription of IME1. Therefore, the effect of Mck1 on the transcription of IME1 is most probably not mediated by PKA. Mck1 is subject to 15
autophosphorylation, including on a conserved tyrosine (Y199) (Rayner et al., 2002). Phosphorylation of this tyrosine residue in Mck1, similar to other GSK3β homologs, is required for its kinase activity on exogenous substrates, but not for autophosphorylation (Rayner et al., 2002). The Ptp2 and Ptp3 tyrosine phosphatases are required for Mck1 dephosphorylation (Zhan et al., 2000). Deletion of either PTP2 or PTP3 has no effect on meiosis, however, the double mutant ptp2∆ ptp3∆ is sporulation deficient, it arrests in meiosis prior to premeiotic DNA replication, with a significant reduction in the expression of IME1 and IME2, and no expression of middle or late meiosis-specific genes (Zhan et al., 2000). A third tyrosine phosphatase, Yvh1, might contribute to this regulation (Guan et al., 1992). Deletion of YVH1 leads to minor effects on the transcription of IME1, a reduced transcription of IME2, and a reduction in the efficiency of asci formation (Park et al., 1996), but in the double mutant yvh1∆ ptp2∆ sporulation is almost diminished (Park et al., 1996). Thus, the effect of these tyrosine phosphatases on meiosis may be partially mediated through Mck1. The transcription of YVH1 is induced upon nitrogen depletion, suggesting that it might be involved with transmitting the nitrogen signal (Park et al., 1996). Over expression of Mck1 suppresses the sporulation defect of cells deleted for TPS1 (De Silva- Udawatta and Cannon, 2001). TPS1 encodes one of the subunits of the trehalose phosphate synthase complex (Reinders et al., 1997). Thus, Tps1 may either regulate Mck1, or suppression of mck1∆ by Tps1 is due to unrelated increase in the level of Ime1. The region in IME1 regulated by Mck1 and its mode of function is not known. However, the additive effects of mutations in MCK1, MDS3, PMD1, RIM1 and IME4 suggest that these genes affect different regulatory elements in the IME1 promoter (Su and Mitchell, 1993b). 2. Tup1/Ssn6. The Tup1/Ssn6 complex functions as a general transcriptional repressor upon recruitment by specific DNA-binding proteins (Keleher et al., 1992). These proteins are also negative regulators for the transcription of IME1 (Mizuno et al., 1998), but the specific DNAbinding protein that tethers them to IME1 is not known. Two regions in IME1 promoter respond to Tup1, the first one is from -914 to – 621 and the second from -1215 to –915 (Mizuno et al., 1998), functioning as URS in the presence of Tup1, and UAS in the absence of Tup1, respectively (Mizuno et al., 1998). Since these regions carry the IREd and IREu repeated elements (Fig. 3) that function as repression and activation sequences, respectively, it should be interesting to determine if the Tup1/Ssn6 complex mediates its effect through these elements, and whether Sok2 is the DNA-binding protein that recruits them to these elements. 16
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: In the absence of glucose Sok2 does
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 and 30: heterologous promoter does not supp
Page 31 and 32: expressed only in the absence of gl
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
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