Early Cell Cycle Box-Mediated Transcription ofCLN3 and SWI4 Contributes to the Proper Timing of the G1-to-S Transition in Budding Yeast

MacKay, Vivian L.; Mai, Bernard; Waters, L.; Breeden, Linda

doi:10.1128/mcb.21.13.4140-4148.2001

Cited by 50 publications

(35 citation statements)

References 51 publications

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“…Third, we tested the IPs for enrichment of a fragment overlapping the CLN3 promoter and coding sequence ( Figure 4A). The CLN3 promoter possesses no canonical MCBs or SCBs and is not a G1/S-regulated gene (Spellman et al 1998;Mackay et al 2001). No specific binding of Swi4 to the CLN3 fragment was detected; however, there was variable enrichment of CLN3 in IPs from the Mbp1-tagged strain.…”

Section: Resultsmentioning

confidence: 90%

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

2005

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In budding yeast, many genes are induced early in the cell cycle. Induction of these genes has been predominantly attributed to two transcription factors, Swi4-Swi6 (SBF) and Mbp1-Swi6 (MBF). Swi4 and Mbp1 are related DNA-binding proteins with dissimilar target sequences. For most G1/S-regulated genes that we tested in a cdc20 block-release protocol for cell-cycle synchronization, removal of both Swi4 and Mbp1 was necessary and sufficient to essentially eliminate cell-cycle-regulated expression. Detectable SBF or MBF binding sites (SCBs or MCBs) in the promoters or available genome-wide promoter occupancy data do not consistently explain this functional overlap. The overlapping ability of these transcription factors to regulate many promoters with very similar cell-cycle kinetics may provide robustness to the G1/S transcriptional response, but poses a puzzle with respect to promoter-transcription factor specificity. In addition, for some genes, deletion of Mbp1 or Swi4 enhances transcription, suggesting that these factors can also function as transcriptional repressors. Finally, we observe residual G1/S transcriptional regulation in the absence of Swi4 and Mbp1.

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Section: Resultsmentioning

confidence: 90%

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

2005

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“…All strains are derivatives of W303a (a ade2-1 his3-11 leu2-3,112 trp1-1 ura3 can1-100 ssd1-d). BY2278 (cln3ecb-5) and BY2690 (cln3ecb-6) contain mutations in five or six of the potential CLN3 ECB sequences, respectively, and have been previously described (28). Cells were grown in yeast extractpeptone (YEP) media supplemented with 2% carbon source as indicated.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the ECB Binding Complex Responsible for the M/G₁-Specific Transcription of CLN3 and SWI4

Mai

Miles

Breeden

2002

Molecular and Cellular Biology

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The transcription factor Mcm1 is regulated by adjacent binding of a variety of different factors regulating the expression of cell-type-specific, cell cycle-specific, and metabolic genes. In this work, we investigate a new class of Mcm1-regulated promoters that are cell cycle regulated and peak in late M-early G 1 phase of the cell cycle via a promoter element referred to as an early cell cycle box (ECB). Gel filtration experiments indicate that the ECB-specific DNA binding complex is over 200 kDa in size and includes Mcm1 and at least one additional protein. Using DNase I footprinting in vitro, we have observed protection of the ECB elements from the CLN3, SWI4, CDC6, and CDC47 promoters, which includes protection of the 16-bp palindrome to which Mcm1 dimers are known to bind as well as protection of extended flanking sequences. These flanking sequences influence the stability and the variety of complexes that form on the ECB elements, and base substitutions in the protected flank affect transcriptional activity of the element. Chromatin immunoprecipitations show that Mcm1 binds in vivo to ECB elements throughout the cell cycle and that binding is sensitive to carbon source changes.Mcm1, its mammalian counterpart (serum response factor), and other members of the MADS box family of transcription factors share a 56-amino-acid MADS box, carrying a conserved DNA binding and dimerization domain (42). They are combinatorial transcription factors in that they typically bind adjacent to and derive their regulatory specificity from other DNA binding and/or accessory factors (3,20,42). Figure 1 depicts four classes of transcription complexes that include Mcm1. Depending upon the context, Mcm1 can be a component of an activating or a repressing complex, and these complexes can be regulated by specific events in the cell cycle or in response to internal or external cues. For example, repression of a-specific genes in ␣ haploid and a/␣ diploid cells involves cooperative binding of ␣2 and Mcm1 to adjacent binding sites (22,39). Then ␣2 recruits the Ssn6/Tup1 repressor complex to the site and prevents transcription (16). In contrast, ␣-specific genes are induced by Mcm1 and another ␣-specific transcription factor, ␣1 (43). In a cells, ␣2 is not produced, so the repressing complex cannot be formed. In that case, Mcm1 cooperates with another haploid-specific transcription factor, Ste12, to activate transcription and confer pheromone responsiveness to these promoters (12,14).Mcm1 is also involved in the regulation of arginine metabolism (not shown), where it forms a complex with Arg82 and two other DNA binding proteins: Arg80 and -81 (13, 33). The presence of arginine is sensed by Arg82 and results in the activation of transcription of catabolic enzymes and repression of anabolic enzymes, depending upon the context. Arg82 has recently been identified as an inositol-1,4,5-triphosphate kinase, and this discovery suggests a direct connection between the lipid signaling cascade and gene regulation in yeast (35).Mcm1 also plays a rol...

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“…Mcm1p is another transcription factor reported to mediate CLN3 transcription in a cell-cycle-dependent manner (56)(57)(58)(59). We tested the binding of Mcm1p to the CLN3 promoter across the YMC.…”

Section: Rap1p and Fhl1p Are Transcription Factors That May Regulate mentioning

confidence: 99%

Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae

Shi

2013

Proc. Natl. Acad. Sci. U.S.A.

127

125

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In budding yeast cells, nutrient repletion induces rapid exit from quiescence and entry into a round of growth and division. The G1 cyclin CLN3 is one of the earliest genes activated in response to nutrient repletion. Subsequent to its activation, hundreds of cellcycle genes can then be expressed, including the cyclins CLN1/2 and CLB5/6. Although much is known regarding how CLN3 functions to activate downstream targets, the mechanism through which nutrients activate CLN3 transcription in the first place remains poorly understood. Here we show that a central metabolite of glucose catabolism, acetyl-CoA, induces CLN3 transcription by promoting the acetylation of histones present in its regulatory region. Increased rates of acetyl-CoA synthesis enable the Gcn5p-containing Spt-AdaGcn5-acetyltransferase transcriptional coactivator complex to catalyze histone acetylation at the CLN3 locus alongside ribosomal and other growth genes to promote entry into the cell division cycle.growth control | metabolism | epigenetics T he most basic building blocks of biological organisms are smallmolecule metabolites. In recent years, there has been renewed interest in understanding how the fundamental processes of cell growth and proliferation are coordinated with cellular metabolism. Nutrient-starved yeast cells arrest in a quiescent, or G0, phase of the cell division cycle. Addition of nutrients stimulates exit from the G0 and transition into the G1 phase, and then ∼800 genes are periodically transcribed as a function of the cell cycle (1, 2). CLN3 is observed to be one of the earliest genes transcribed within this set (1-3). Cln3p regulates G1 length by coordinating growth and division and may influence cell size when passing Start, the point at which cells commit to division (4-7). In cln3Δ mutants, cells become larger and stay in the G1 phase longer, resulting in decreased growth and budding rates compared with WT (8, 9) (Fig. S1). Following CLN3 activation, the G1 transcription complexes Swi4p-Swi6p (SBF) and Mbp1-Swi6p (MBF) can be activated by CLN3/CDC28-catalyzed phosphorylation of the SBF inhibitor Whi5p (10-12), and other unknown mechanisms, to enable transcription of over 200 downstream cell-cycle genes (13), including CLN1/2 and CLB5/6. Cln1p and Cln2p can then further enhance SBF-and MBF-dependent G1 transcription through positive feedback mechanisms (14)(15)(16)(17)(18)(19)(20).Although many studies have focused on the mechanisms by which Cln3p regulates G1 transcription, the mechanisms that lead to transcriptional activation of CLN3 itself still remain unresolved. Since the discovery of CLN3 more than 20 y ago (6, 7), the gene and its encoded protein have been reported to be regulated at multiple levels. At the transcriptional level, CLN3 is activated by glucose (21, 22), which is reportedly mediated by Azf1p, a zinc-finger transcription factor (23). Following transcription, CLN3 mRNA availability is regulated by a RNAbinding protein, Whi3p (24). At the translational level, CLN3 is regulated by TOR (target of rapamyc...

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Early Cell Cycle Box-Mediated Transcription ofCLN3 and SWI4 Contributes to the Proper Timing of the G₁-to-S Transition in Budding Yeast

Cited by 50 publications

References 51 publications

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

Characterization of the ECB Binding Complex Responsible for the M/G₁-Specific Transcription of CLN3 and SWI4

Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae

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Early Cell Cycle Box-Mediated Transcription ofCLN3 and SWI4 Contributes to the Proper Timing of the G1-to-S Transition in Budding Yeast

Cited by 50 publications

References 51 publications

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

High Functional Overlap Between MluI Cell-Cycle Box Binding Factor and Swi4/6 Cell-Cycle Box Binding Factor in the G1/S Transcriptional Program in Saccharomyces cerevisiae

Characterization of the ECB Binding Complex Responsible for the M/G1-Specific Transcription of CLN3 and SWI4

Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae

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Early Cell Cycle Box-Mediated Transcription ofCLN3 and SWI4 Contributes to the Proper Timing of the G₁-to-S Transition in Budding Yeast

Characterization of the ECB Binding Complex Responsible for the M/G₁-Specific Transcription of CLN3 and SWI4