ライフサイエンスコーパス: MCM1

1 ed through two DNA-binding factors, Tbf1 and Mcm1.

2 odes a MADS-box protein orthologous to yeast Mcm1.

3 n experiments in the presence and absence of Mcm1.

4 important for transcriptional activation by Mcm1.

5 onsensus sequence obtained in the absence of Mcm1.

6 regulate the essential transcription factor Mcm1.

7 lace of the patch in alpha2 to interact with Mcm1.

8 sites for the DNA-binding proteins Rap1 and Mcm1.

9 d involve combinatorial control of Ste12 and Mcm1.

10 ndently of the gene-specific repressor, ArgR/Mcm1.

11 lpha1 is more complex than simply recruiting Mcm1.

12 lates its own expression in conjunction with Mcm1.

13 egulator of the transcriptional complex ArgR-Mcm1.

14 as required for gene regulation through ArgR-Mcm1.

15 ranscription of the regulators MATalpha1 and MCM1.

16 This plasmid instability in the mcm1-1 mutant can be overcome for a subset of ARSs by th

17 ential ARS activity observed in our previous mcm1-1 mutant experiments 1, by suggesting the relevance

18 Reduced DNA binding activity in the Mcm1-1 mutant protein (P97L) results in selective initia

19 ed in the mcm7-1 mutant and decreased in the mcm1-1 mutant, suggesting that Mcm7 modulates its own ex

20 replicate with different efficiencies in the mcm1-1 mutant.

21 e for efficient replication of ARS120 in the mcm1-1 mutant.

22 three archaeal MCM homologs, here designated MCM1-3, although MCM1 and MCM2 are unusual in having lon

23 n protein alpha2 specifically interacts with Mcm1, a MADS box protein, to bind DNA specifically and r

24 We provide here evidence that Mcm1, a MADS-box protein, is essential for PHO5 mitotic

25 that of the equivalent SAM domain in SRF and MCM1, accounting for the absence of cross-reactivity wit

26 n in yeast, can enhance transcription by the MCM1 activator in hormone-dependent manner, consistent w

27 MADS domain (for MCM1, AG, DEFA and SRF) proteins are regulatory proteins

28 The zinc fingers of ZIC3 and the mcm1, agamous deficiens SRF (MADS) box motif of SRF were

29 MEF2 is an evolutionarily conserved MADS (MCM1, Agamous, Deficiens, and serum response factor) box

30 yte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box tra

31 e myocyte enhancer factor-2 (MEF2) family of MCM1-agamous-deficiens-serum response factor (MADS)-box

32 They share the conserved N-terminal MCM1-agamous-deficiens-serum response factor and MEF2 do

33 FLC encodes a MADS (MCM1/AGAMOUS/DEFICIENS/SRF1) domain transcription factor

34 resence and absence of alpha1 and found that Mcm1 alone shows a reduced DNA-bend at this site compare

35 We analyzed Mcm1-dependent bending of a Mcm1-alpha1 binding site in the presence and absence of

36 t a model in which proper DNA-bending by the Mcm1-alpha1 complex is required for transcriptional acti

37 d the requirement of the cofactor alpha1 for Mcm1-alpha1-dependent transcriptional activation we anal

38 complex is over 200 kDa in size and includes Mcm1 and at least one additional protein.

39 nine substitutions in the MADS box domain of Mcm1 and examined the effects of these mutations in comb

40 e substitutions in the DNA-binding domain of Mcm1 and examined the effects of these mutations in vivo

41 Mcm1 and Fkh1 regulate RE activity in a cells.

42 n protein in association with its cofactors, Mcm1 and Mata1.

43 M homologs, here designated MCM1-3, although MCM1 and MCM2 are unusual in having long and unique N-te

44 examined the effect of mutant alleles of the MCM1 and SLN1 genes and carbon source on expression of t

45 ific requirements for bending differ between Mcm1 and SRF.

46 These proteins bind to Mcm1 and to a typical homeodomain binding site.

47 . kodakarensis strain with the genes TK0096 (MCM1) and TK1361 (MCM2) deleted has been constructed tha

48 R1 was dependent on the transcription factor Mcm1, and expression of a gene with Mcm1 fused to a stro

49 actor binding sites, including that of Reb1, Mcm1, and Rsc3, that cause the local nucleosome depletio

50 t yeast glutamine-rich domains from HAP2 and MCM1 are also transcriptionally active in S. cerevisiae.

51 Our results indicate which residues of Mcm1 are essential for viability and transcriptional reg

52 Our results indicate which residues of Mcm1 are important for viability, transcriptional activa

53 evisiae may be regulated by the occupancy of Mcm1 at replication origins.

54 Here we show that Mcm1 binding is required for both the transcription of t

55 Surprisingly, a 2-bp mutation in the Mcm1 binding site completely abolishes RE activity in MA

56 Mutating a conserved Mcm1 binding site in the C domain diminished replication

57 us binding site, most closely related to the Mcm1 binding site of Saccharomyces cerevisiae.

58 The ECB element contains an Mcm1 binding site to which Mcm1 binds in vitro, and an M

59 Proficient NER influenced PR in the TATA and Mcm1 binding sites by enhancing it, particularly when tr

60 We found that additional Mcm1 binding sites in the C domain of ARS120 that are mi

61 ild-type cells, and increasing the number of Mcm1 binding sites stimulated replication efficiency.

62 ed the yeast genome for all potential alpha2-Mcm1 binding sites.

63 ed DNA-bend at this site compared with other Mcm1 binding sites.

64 Indeed, Mcm7 stimulates Mcm1 binding to the early cell cycle box upstream of the

65 on, which places a constitutive activator on Mcm1-binding sites in vivo, can deregulate ECB-containin

66 Previous work showed that Mcm1 binds constitutively to the MCM7 promoter and regul

67 Using purified Mcm1 protein, we show that Mcm1 binds cooperatively to multiple sites at autonomous

68 MCM1 does not form homohexamers and although MCM1 binds DNA and has ATPase activity, it has only mini

69 ement contains an Mcm1 binding site to which Mcm1 binds in vitro, and an Mcm1-VP16 fusion, which plac

70 Chromatin immunoprecipitations show that Mcm1 binds in vivo to ECB elements throughout the cell c

71 Previous work showed that Mcm1 binds sequences flanking the minimal functional dom

72 Whereas Mcm1 binds these promoters constitutively, Mcm7 is recru

73 minal extension had no detectable effects on MCM1 but increased the helicase activity of MCM2.

74 Thus, the alpha1/Mcm1 coactivators did not overcome repression by occludi

75 on of a heterologous promoter and the alpha2-Mcm1 complex binds to the site in vitro.

76 pressor sites in vivo or bound by the alpha2-Mcm1 complex in vitro.

77 uence requirements for binding by the alpha2-Mcm1 complex, we have searched the yeast genome for all

78 The Matalpha2-Mcm1 complex, which normally represses a-specific genes,

79 alpha2-Mcm1 complexes repress a cell-specific gene expression i

80 n MATalpha cells by binding of the Matalpha2-Mcm1 corepressor to a site within the RE.

81 We analyzed Mcm1-dependent bending of a Mcm1-alpha1 binding site in

82 nserved CC(A/T)6GG site significantly reduce Mcm1-dependent DNA bending, while these substitutions ha

83 nd a corresponding decrease in expression of Mcm1-dependent genes.

84 SLN1 also activates an MCM1-dependent reporter gene, P-lacZ, but this function

85 ause a 5-fold increase in the activity of an Mcm1-dependent reporter, whereas deletion of SLN1 causes

86 eterologous promoter and assaying for alpha2-Mcm1-dependent repression in vivo and DNA-binding affini

87 fic genes and two other sites have an alpha2-Mcm1-dependent role in determining the direction of mati

88 protection of the 16-bp palindrome to which Mcm1 dimers are known to bind as well as protection of e

89 oth the serum response factor-DNA and alpha2-Mcm1-DNA crystal structures, suggesting that these resid

90 In contrast, MCM1 does not form homohexamers and although MCM1 binds

91 O5 mitotic activation, (ii) demonstrate that Mcm1-Fkh2 can function combinatorially with other activa

92 The Mcm1-Fkh2 complex, first shown to transactivate genes wi

93 coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are suff

94 dicating that DNA bending may have a role in Mcm1 function in the cell.

95 J. Deschenes, and J. S. Fassler showed that Mcm1 function is affected by mutations in the SLN1 gene,

96 n factor Mcm1, and expression of a gene with Mcm1 fused to a strong transcriptional activation domain

97 on of PIS1 gene expression required both the MCM1 gene and the MCEs, whereas the SLN1 gene was requir

98 of these mutations can be suppressed if the MCM1 gene is expressed from a high-copy-number plasmid.

99 We conclude that the role of Mcm1 in RE is to open chromatin around the conserved dom

100 ified that specifies direct interaction with Mcm1 in the absence of DNA.

101 results suggest that threshold occupancy of Mcm1 in the C domain of telomeric ARSs is required for e

102 ere, we identify Mcm7 as a novel cofactor of Mcm1 in the regulation of MCM7 expression.

103 is required for cooperative DNA binding with Mcm1 in vitro and for transcriptional repression in vivo

104 To explore the protein-DNA interactions of Mcm1 in vivo and in vitro, we have introduced an extensi

105 SCYJL170C is repressed by alpha2-Mcm1 in vivo and therefore using this method we have ide

106 al MADS-box transcription factors, including Mcm1, induce DNA bending and there is evidence the prope

107 teraction sites for alpha2 corepressors: the Mcm1 interaction site in the central alpha2 linker and t

108 For example, in Saccharomyces cerevisiae, Mcm1 interacts with the forkhead transcription factor Fk

109 Mcm1 interacts with the Matalpha1 protein to activate th

110 Mcm1 is a transcription factor that is also required for

111 alpha-specific genes in vivo and found that Mcm1 is able to bind to the promoters of alpha-specific

112 In this study, we report that Mcm1 is an abundant protein that associates globally wit

113 MCM1 is an essential gene in the yeast Saccharomyces cer

114 Mcm1 is an essential protein required for the efficient

115 Thus, Mcm1 is critically responsible for the activation as wel

116 hoto-cross-linking experiments indicate that Mcm1 is in close proximity to functional groups in the m

117 sponsive to osmotic stress: a new isoform of Mcm1 is induced by NaCl or KCl; this result establishes

118 We show that Mcm1 is localized at replication origins and plays an im

119 The transcription factor Mcm1 is regulated by adjacent binding of a variety of di

120 This result shows that the DNA bending by Mcm1 is sequence dependent and that the base-specific re

121 Minichromosome maintenance protein 1 (Mcm1) is required for efficient replication of autonomou

122 Mcm1, particularly the notion that a unique Mcm1 isoform could be required for regulation of a speci

123 by NaCl or KCl; this result establishes that Mcm1 itself is regulated.

124 s suggest that within the same region of the Mcm1 MADS box domain, there are different requirements f

125 de evidence that the N-terminal extension of Mcm1 may have considerable conformational freedom, possi

126 tor for the expression of replication genes, Mcm1 may influence the local structure of replication or

127 mutants at positions which are critical for Mcm1-mediated DNA bending that have a slow-growth phenot

128 , most mutations have little or no effect on Mcm1-mediated repression in combination with the alpha 2

129 for the activation as well as the Matalpha2-Mcm1-mediated repression of RE activity.

130 operator site and examined their effects on Mcm1-mediated transcriptional regulation and DNA-binding

131 vide evidence that the replication defect of mcm1 mutants can be suppressed by ectopic CDC6 transcrip

132 We find that mcm1 mutations can confer either reduced or enhanced sur

133 ve series of base pair substitutions into an Mcm1 operator site and examined their effects on Mcm1-me

134 osomes are positioned adjacent to the alpha2-Mcm1 operator under conditions of repression and that Tu

135 ioning of nucleosomes adjacent to the alpha2-Mcm1 operator, nucleosomes are not positioned adjacent t

136 The implications of multiple species of Mcm1, particularly the notion that a unique Mcm1 isoform

137 We also show here that Mcm1 plays an important role in the response to stress c

138 Mcm1 protein acts on a large number of distinctly regula

139 Because the Mcm1 protein interacts with both the Sln1 and the Gal11

140 The yeast Mcm1 protein is a founding member of the MADS-box family

141 The yeast Mcm1 protein is a member of the MADS box family of trans

142 The yeast Mcm1 protein is a member of the MADS box family of trans

143 Furthermore, Mcm1 protein is a target of a signal transduction system

144 The Saccharomyces cerevisiae Mcm1 protein is an essential multifunctional transcripti

145 We show here that Mcm1 protein is phosphorylated in vivo.

146 alpha2 (alpha2) repressor interacts with the Mcm1 protein to turn off a-cell type-specific genes in t

147 Several (more than eight) isoforms of Mcm1 protein, resolved by isoelectric focusing, are pres

148 Using purified Mcm1 protein, we show that Mcm1 binds cooperatively to m

149 oter includes sequences (MCEs) that bind the Mcm1 protein.

150 The alpha2 and Mcm1 proteins bind DNA as a heterotetramer to repress tr

151 lated MADS-box transcription factors SRF and MCM1 provide a molecular explanation for modulation of s

152 In this work, we investigate a new class of Mcm1-regulated promoters that are cell cycle regulated a

153 d trigger the Sln1-dependent activity of the Mcm1 reporter.

154 The MADS-box transcription factors SRF and Mcm1 represent paradigms for such regulation through the

155 action of the Mata1-Matalpha2 and Matalpha2-Mcm1 repressors.

156 required for regulation of a specific set of Mcm1's target genes, are discussed.

157 ments in yeast (STE12, GAL4, RAP1, SCB, MCB, MCM1, SFF, and SWI5), and predicted two motif patterns f

158 We compared five natural alpha2-Mcm1 sites with an alpha2-Mcm1 symmetric consensus site

159 ive natural alpha2-Mcm1 sites with an alpha2-Mcm1 symmetric consensus site (AMSC) for their relative

160 inding specificity of alpha2 in complex with Mcm1, symmetric substitutions at each position in the al

161 d with transcriptional activation of MBF and Mcm1 target genes, respectively.

162 Most of the mutations in Mcm1 that are lethal affect DNA-binding affinity.

163 tive amino acid substitutions of residues in Mcm1 that directly contact alpha 2 do not significantly

164 results demonstrate that in the presence of Mcm1 the sequence specificity of alpha2 is extended to t

165 In the presence of Mcm1, the consensus sequences obtained were extended and

166 NA bending and transcriptional activation by Mcm1, they have a relatively small effect on the DNA-bin

167 rther, a mutation that alters the ability of Mcm1 to act with Matalpha2 in repressing a-specific gene

168 alanine substitutions affect the ability of Mcm1 to activate transcription alone or in combination w

169 al activation we analyzed the recruitment of Mcm1 to the promoters of alpha-specific genes in vivo an

170 associate with opposite sides of the dimeric Mcm1 transcription factor but nevertheless compete for b

171 Ssn6-repressed SUC2 gene, but not the alpha2-Mcm1-Tup1-Ssn6-repressed STE2 gene.

172 Our results show that Mcm1 uses a mechanism to contact the DNA that has some s

173 ng site to which Mcm1 binds in vitro, and an Mcm1-VP16 fusion, which places a constitutive activator

174 Substitution of residues in Mcm1 which are highly conserved among the MADS-box prote

175 hase expression of the MADS box protein gene MCM1, which has been implicated in the regulation of opa

176 essential MADS-box transcriptional regulator Mcm1, which is found in all fungi and regulates a large

177 ccharomyces cerevisiae, the MADS-box protein Mcm1, which is highly related to mammalian SRF (serum re