Transcriptional regulation of meiosis in budding yeast

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3. Yhp1. YHP1 encodes a homeodomain protein that binds to the UASv element in IME1 promoter, between -702 to –675 (Fig. 3) (Kunoh et al., 2000). This 28 bp element by itself does not function as a UAS, but when tethered to heterologous reporter genes, it causes a 2-fold reduction in expression, suggesting that Yhp1 functions as a repressor (Kunoh et al., 2000). The mode by which Yhp1 represses transcription is not known, but its effect is independent of the Tup1/Ssn6 repression complex (Kunoh et al., 2000). The transcription of YHP1 is reduced in vegetative cells grown in the presence of acetate as the sole carbon source in comparison to glucose (Kunoh et al., 2000), implying that it might transmit a glucose signal. However, deletion of YHP1 has no effect on either the transcription of IME1, or on the ability of cells to enter and complete meiosis and sporulation (Kunoh et al., 2000). 4. The Swi/Snf chromatin remodeling complex. Two components of the Swi/Snf complex, Snf2 and Swi1 are required for high-level expression of IME1 (Yoshimoto et al., 1993). This complex is involved with transcriptional activation of genes to whom it is tethered through interaction with specific activation domains [for review see (Carlson and Laurent, 1994)]. E. Positive and Negative feedback regulation. The transcription of IME1 is subject to positive regulation. Over expression of Ime1 leads to increase in the level of ime1-lacZ, through its effect on the function of IREu (Shenhar and Kassir, 2001). The effect of Ime1 on additional elements has not yet been determined. This autoregulation is required to relieve repression by Sok2. This is deduced from the following results: i. Expression of IREu-his4-lacZ is substantially reduced in diploid cells deleted for IME1 (Shenhar and Kassir, 2001), ii. Gal4(bd)-Sok2 represses the transcription of GAL1UAS-HIS4 UAS - his4-lacZ in SD but has no repression activity in SA (Shenhar and Kassir, 2001). However, in diploid cells deleted for IME1 the transcription of the reporter gene is repressed in both SD and SA media (Shenhar and Kassir, 2001). Since in the presence of glucose Ime1 is not expressed, it is not surprising that the effect of Ime1 is observed only in SA. As will be detailed in section IVB2, Ime1 does not bind directly to DNA, and is recruited to the DNA by interacting with a DNA-binding protein. Since the N-terminal domain of Sok2 is also required to relieve repression in SA, it is tempting to suggest that Ime1 associates with the N-terminal domain of Sok2. No information on possible associations between these two proteins has yet been reported. The transcription of IME1 as well as the steady-state level of Ime1 protein in meiotic conditions is transient, when induced upon a shift to SPM, the level of IME1 peaks at about 6-8 17
hours in SPM, followed by a decline (Guttmann-Raviv and Kassir, 2002; Kassir et al., 1988; Shefer-Vaida et al., 1995). This transient transcription depends on both Ime1 and Ime2 (Guttmann-Raviv and Kassir, 2002; Mitchell et al., 1990; Shefer-Vaida et al., 1995; Smith and Mitchell, 1989; Yoshida et al., 1990). This negative feedback effect is on transcription of IME1 rather than the stability of the mRNA, since insertions of two separate regions, -621 to –924 and – 924 to –1368 (Fig. 3) upstream of cyc1-lacZ exhibit the same feedback regulation (Shefer-Vaida et al., 1995). Ime1 is a non-stable protein that is degraded by the proteasome and whose half-life depends on Ime2 (Guttmann-Raviv and Kassir, 2002). IME2 encodes a meiosis-specific protein kinase that interacts with Ime1 and phosphorylates it in vitro (Guttmann-Raviv and Kassir, 2002). We suggest that the effect of Ime2 on shutting down the transcription of IME1 is due to its effect on the stability of Ime1 protein. In the presence of Ime2, degradation of Ime1 would lead to the establishment of Sok2 repression and silencing. On the other hand, in cells deleted for IME2, accumulation of Ime1 leads to continues positive autoregulation, and increase in its transcription, and consequently the availability of Ime1 protein (Guttmann-Raviv and Kassir, 2002). F. Summary. IME1 encodes the master regulator required to open a developmental pathway, that of meiosis, in S. cerevisiae. It is not surprising, therefore, that its transcription is regulated by an unusual large 5’ region that is subject to multiple regulations. Fig. 9 is a summary of the results described above, on the current knowledge on how the meiotic signals are transmitted to IME1. A combinatorial effect of at least 10 distinct elements ensures that IME1 will be transcribed only under the appropriate conditions, namely in MATa/MATα diploids, the absence of glucose, the presence of acetate, and nitrogen depletion. Two negative elements, UCS3 and UCS4 restrict elevated transcription of IME1 to cells expressing Mata1 and Matα2 peptides. In vegetative growth media with glucose as the sole carbon source IME1 is silent. This regulation is accomplished by using 4 distinct elements, UCS1 IREu UASru, and UASv, whose function as repression elements is mediated through distinct signal transduction pathways. In acetate growth media a low level of transcription is accomplished by the positive activity of UASru, IREu, UASrm and UASv that is opposed by negative regulation from UCS1 as well as from three constitutive URS elements, URSu, URSd and IREd. Upon nitrogen depletion, relief of UCS1 repression promotes an increase in transcription. 18
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: autophosphorylation, including on a
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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