LEU3 of Saccharomyces cerevisiae activates multiple genes for branched-chain amino acid biosynthesis by binding to a common decanucleotide core sequence.

Friden, Phillip M.; Schimmel, Paul

doi:10.1128/mcb.8.7.2690

Cited by 93 publications

(84 citation statements)

References 37 publications

(35 reference statements)

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“…To do so, we calculate the average S N score for each 10-mer present in the Leu3_YPD sequence-set ( Figure 3A). Leu3 is known to recognize the 10-mer CCGGNNCCGG, with a slight preference for CCGGTACCGG [15,16], and indeed we find that fewer than 10% of 10-mers score higher than CCGGTACCGG, revealing that the prior N is assigning a higher prior probability to positions containing the true motif.…”

Section: Nucleosome Occupancy Predictions Used Directly Only Marginalsupporting

confidence: 50%

A nucleosome-guided map of transcription factor binding sites in yeast

2005

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Finding functional DNA binding sites of transcription factors (TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical challenge: many more matches to known TF motifs occur in the genome than are actually functional. However, information about chromatin structure may help to identify the functional sites. In particular, it has been shown that active regulatory regions are usually depleted of nucleosomes, thereby enabling TFs to bind DNA in those regions. Here, we describe a novel motif discovery algorithm that employs an informative prior over DNA sequence positions based on a discriminative view of nucleosome occupancy. When a Gibbs sampling algorithm is applied to yeast sequence-sets identified by ChIP-chip, the correct motif is found in 52% more cases with our informative prior than with the commonly used uniform prior. This is the first demonstration that nucleosome occupancy information can be used to improve motif discovery. The improvement is dramatic, even though we are using only a statistical model to predict nucleosome occupancy; we expect our results to improve further as highresolution genome-wide experimental nucleosome occupancy data becomes increasingly available.

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Section: Nucleosome Occupancy Predictions Used Directly Only Marginalsupporting

confidence: 50%

A nucleosome-guided map of transcription factor binding sites in yeast

2005

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“…LEU3 encodes a zinc-finger transcription factor that regulates genes involved in the biosynthesis and uptake of branched-chain amino acids (Friden and Schimmel 1988;Nielsen et al 2001). Strain BY4742 is a leucine auxotroph, and its growth depends on external leucine.…”

Section: Resultsmentioning

confidence: 99%

Global Screening of Genes Essential for Growth in High-Pressure and Cold Environments: Searching for Basic Adaptive Strategies Using a Yeast Deletion Library

Abe

Minegishi

2008

Genetics

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Microorganisms display an optimal temperature and hydrostatic pressure for growth. To establish the molecular basis of piezo-and psychroadaptation, we elucidated global genetic defects that give rise to susceptibility to high pressure and low temperature in Saccharomyces cerevisiae. Here we present 80 genes including 71 genes responsible for high-pressure growth and 56 responsible for low-temperature growth with a significant overlap of 47 genes. Numerous previously known cold-sensitive mutants exhibit marked high-pressure sensitivity. We identified critically important cellular functions: (i) amino acid biosynthesis, (ii) microautophagy and sorting of amino acid permease established by the exit from rapamycin-induced growth arrest/Gap1 sorting in the endosome (EGO/GSE) complex, (iii) mitochondrial functions, (iv) membrane trafficking, (v) actin organization mediated by Drs2-Cdc50, and (vi) transcription regulated by the Ccr4-Not complex. The loss of EGO/GSE complex resulted in a marked defect in amino acid uptake following high-pressure and low-temperature incubation, suggesting its role in surface delivery of amino acid permeases. Microautophagy and mitochondrial functions converge on glutamine homeostasis in the target of rapamycin (TOR) signaling pathway. The localization of actin requires numerous associated proteins to be properly delivered by membrane trafficking. In this study, we offer a novel route to gaining insights into cellular functions and the genetic network from growth properties of deletion mutants under high pressure and low temperature.

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“…Leu3 functions as a homodimer to control the transcription of genes involved in branched-chain amino acid metabolism, and binds to the palindromic consensus site CCGGNNCCGG (Friden and Schimmel 1988). To catalog all sites of potential interaction between Leu3 and genomic DNA, we scanned the genome for Leu3-binding motifs (see Supplemental Methods).…”

Section: Most Leu3 Motifs In the Genome Occur By Chancementioning

confidence: 99%

Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection

Liu¹,

Lee²,

Granek³

et al. 2006

Genome Res.

128

121

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Sequence motifs that are potentially recognized by DNA-binding proteins occur far more often in genomic DNA than do observed in vivo protein–DNA interactions. To determine how chromatin influences the utilization of particular DNA-binding sites, we compared the in vivo genome-wide binding location of the yeast transcription factor Leu3 to the binding location observed on the same genomic DNA in the absence of any protein cofactors. We found that the DNA-sequence motif recognized by Leu3 in vitro and in vivo was functionally indistinguishable, but Leu3 bound different genomic locations under the two conditions. Accounting for nucleosome occupancy in addition to DNA-sequence motifs significantly improved the prediction of protein–DNA interactions in vivo, but not the prediction of sites bound by purified Leu3 in vitro. Use of histone modification data does not further improve binding predictions, presumably because their effect is already manifest in the global histone distribution. Measurements of nucleosome occupancy in strains that differ in Leu3 genotype show that low nucleosome occupancy at loci bound by Leu3 is not a consequence of Leu3 binding. These results permit quantitation of the epigenetic influence that chromatin exerts on DNA binding-site selection, and provide evidence for an instructive, functionally important role for nucleosome occupancy in determining patterns of regulatory factor targeting genome-wide.

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LEU3 of Saccharomyces cerevisiae activates multiple genes for branched-chain amino acid biosynthesis by binding to a common decanucleotide core sequence.

Cited by 93 publications

References 37 publications

A nucleosome-guided map of transcription factor binding sites in yeast

A nucleosome-guided map of transcription factor binding sites in yeast

Global Screening of Genes Essential for Growth in High-Pressure and Cold Environments: Searching for Basic Adaptive Strategies Using a Yeast Deletion Library

Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection

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