Transcriptional regulation of meiosis in budding yeast

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Full expression of Ime1 in S288C strains deleted for RME1 or UCS3 and UCS4 does not lead to complete sporulation (Kassir et al., 1988; Sagee et al., 1998), suggesting that the Mata1 Matα2 proteins might be required for a downstream meiotic event. On the other hand, in SK1 background, this is not the case, and the MATa1 and MATα2 alleles are required only for the transcription of IME1 (Covitz and Mitchell, 1993). There are many reported cases of phenotypic differences between SK1 and other strains, i.e. S288C or W303. Genomic DNA hybridization reveals the presence of many deletions and polymorphisms between these strains (Primig et al., 2000). Thus, the discrepancy between results is attributed to the absence of some functions in the different strains. 1. Genes whose products transmit the MAT signal to IME1 and meiosis. Three genes are known to transmit the MAT signal to IME1 and meiosis: RME1, IME4, and RES1. 1.1. RME1. RME1 encodes a Zinc-finger DNA-binding protein (Covitz et al., 1991; Shimizu et al., 1997a) that is a negative regulator for the transcription of IME1 and meiosis in cells carrying only one of the MAT alleles (Kassir et al., 1988; Kassir and Simchen, 1976; Mitchell and Herskowitz, 1986; Rine et al., 1981). Recessive mutations in RME1 and deletion of RME1 lead to complete expression of IME1 and sporulation in mata1/MATα, MATa/MATa and MATα/MATα strains (Kassir et al., 1988; Kassir and Simchen, 1976; Mitchell and Herskowitz, 1986). Haploid cells carrying the rme1-1 mutation complete premeiotic DNA replication, but arrest as mono nucleate cells without loss of viability (Kassir and Simchen, 1976). This is most probably due to the pachytene checkpoint mechanism that monitors lack of synapsis and/or recombination [for review on this checkpoint see (Roeder and Bailis, 2000)]. In MATa/MATα strains relief of repression is due to the substantial reduction (10 to 20-fold) in the level of RME1 mRNA and protein [(Mitchell and Herskowitz, 1986), and L. Johnston, personal communication]. The Mata1/Matα2 complex binds to a specific element in the promoter of RME1 repressing its transcription (Goutte and Johnson, 1988; Johnson and Herskowitz, 1985; Li et al., 1995; Stark and Johnson, 1994). Rme1 binds the IME1 5’ region to two sites localized within UCS4, at -2040 to –2030 and – 1959 to –1949 (Shimizu et al., 1998). The consensus sequence for binding is GWACCTCAARA (Shimizu et al., 1998). The presence of these two binding sites; defined as the RRE and the modulation element (Covitz and Mitchell, 1993), is required to repress the transcription of IME1. Deletion or mutations in a single site cause only partial derepression (Shimizu et al., 1998). Moreover, deletion of both sites does not lead to complete relief of repression, (Shimizu et al., 1998), probably due to the repression activity of the UCS3 site (Sagee et al., 1998). Insertion of 7
the UCS4 element upstream of the CYC1 UAS results in 17-fold repression, depending on overexpression of Rme1, as well as on the presence of both the RRE and the modulation sites (Covitz and Mitchell, 1993). Unlike the intact IME1 gene, repression dependent on over-expression of Rme1 and dependence on MAT was not reported. It is not surprising, therefore, that in this heterologous system repression is accomplished by sequestering the binding of a transcriptional activator (Shimizu et al., 1997b). The mode by which Rme1 represses transcription of IME1 is not known, however, it repression activity depends on Sin4 and Rgr1 (Covitz et al., 1994), two components of the RNA polymerase SRB mediator complex (Myer and Young, 1998). These proteins are not required for the stability of Rme1 (Covitz et al., 1994), or it’s binding to DNA (Shimizu et al., 1998). Rme1 also functions as a transcriptional activator; it activates the transcription of CLN2 whose promoter includes Rme1’s binding site (Toone et al., 1995). Accordingly, Rme1 also activates the transcription of CYC1 and HIS3 when artificially tethered to their promoters (Covitz and Mitchell, 1993; Covitz et al., 1994). The transcription of RME1 is mainly induced in G1 (Frenz et al., 2001), suggesting that although this gene is non-essential, it might contribute to the high level expression of Cln2 at this stage in the cell cycle. Transcriptional activation is independent of Rgr1 or Sin4 (Blumental-Perry et al., 2002), although the function of Rme1 as an activator or repressor is mediated through the same domain (Blumental-Perry et al., 2002). These results suggest that the function of Rme1 is determined by interacting proteins binding to nearby DNA sites. The effect of MAT on the transcription of IME1 is evident only upon nitrogen depletion; In SA media the level of IME1 mRNA is low and identical in haploid and MATa/MATα diploid cells (Kassir et al., 1988), and only SPM and in MATa/MATα that IME1 is fully induced. Moreover, since nitrogen depletion induces the transcription of RME1 (Frenz et al., 2001), it is possible that Rme1 represses transcription only in the absence of nitrogen. This hypothesis predicts that in the absence of Rme1, initiation of meiosis will not depend on nitrogen depletion. However, cells where either RME1 or UCS3 along with UCS4 (the sites mediating the MAT signal) have been deleted, induce meiosis only upon nitrogen depletion (Kassir and Simchen, 1976; Sagee et al., 1998). The effect of Rme1 is mediated through one of two mechanisms: by direct binding and repression of IME1, and by activation of CLN2 transcription (Frenz et al., 2001; Toone et al., 1995). The increase in activity of the Cln/Cdc28 complex could result in an increase in phosphorylation of Ime1, and its sequestering from the nucleus (Colomina et al., 1999). Consequently, the reduction in positive autoregulation, would lead to a decrease in the level of IME1 mRNA. 8
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: et al., 2000). On the other hand, i
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 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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Transcriptional regulation of meiosis in budding yeast

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