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Cited by 45Antifungal resistance and susceptibilityFungal and yeast genetics researchYeasts and Rust Fungi Studies

Identification of Genomic Binding Sites for Candida glabrata Pdr1 Transcription Factor in Wild-Type and ρ 0 Cells

Open access
Paul, Sanjoy, Bair, Thomas B., Moye-Rowley, W. Scott·2014·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.03921-14PMC PMC4249425
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Abstract

The fungal pathogen Candida glabrata is an emerging cause of candidiasis in part owing to its robust ability to acquire tolerance to the major clinical antifungal drug fluconazole. Similar to the related species Candida albicans , C. glabrata most typically gains azole tolerance via transcriptional induction of a suite of resistance genes, including a locus encoding an ABCG-type ATP-binding cassette (ABC) transporter that is referred to as CDR1 in Candida species. In C. glabrata , CDR1 expression is controlled primarily by the activity of a transcriptional activator protein called Pdr1. Strains exhibiting reduced azole susceptibility often contain substitution mutations in PDR1 that in turn lead to elevated mRNA levels of target genes with associated azole resistance. Pdr1 activity is also induced upon loss of the mitochondrial genome status and upon challenge by azole drugs. While extensive analyses of the transcriptional effects of Pdr1 have identified a number of genes that are regulated by this factor, we cannot yet separate direct from indirect target genes. Here we used chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) to identify the promoters and associated genes directly regulated by Pdr1. These genes include many that are shared with the yeast Saccharomyces cerevisiae but others that are unique to C. glabrata , including the ABC transporter-encoding locus YBT1 , genes involved in DNA repair, and several others. These data provide the outline for understanding the primary response genes involved in production of Pdr1-dependent azole resistance in C. glabrata .

AI snapshot

Written from the paper’s full text.

TL;DR

ChIP-seq was used to identify promoters directly bound by *Candida glabrata* Pdr1 in wild-type (ρ+) and mitochondrial-genome-loss (ρ0) cells, yielding a minimal set of 25 Pdr1 target genes. The direct Pdr1 regulon overlaps with the *Saccharomyces cerevisiae* Pdr network but includes *C. glabrata*-specific targets such as *YBT1*, *QDR2*, and DNA repair genes.

Key findings

  • Anti-Pdr1 ChIP-seq identified 25 genes with reproducible promoter enrichment in ρ0 versus ρ+ cells; 16 of 25 were also enriched with anti-TAP Pdr1.
  • The target set includes shared Pdr-regulon genes such as *CDR1*, *PDH1*, *SNQ2*, *YOR1*, *PDR16*, *RTA1*, *RSB1*, *IPT1*, and *RPN4*, plus *C. glabrata*-specific or newly implicated genes including *YBT1*, *QDR2*, *REV1*, *MEC3*, *PUP1*, *ATF2*, and *NCE103*.
  • ρ0 induction values from the accompanying dataset ranged widely, e.g., *PUP1* 57×, *YOR1* 22×, *PDH1* 18×, *CAGL0A01650g* 12×, *RTA1* 12×, *ATF2* 10×, *MEC3* 9×, and *CDR1* 4×.
  • MEME analysis found a promoter motif closely related to the *S. cerevisiae* pleiotropic drug resistance response element (PDRE), supporting a conserved PDRE-like element in *C. glabrata*.

Methods

  • Isogenic *C. glabrata* ATCC 2001 strains were used, including a *pdr1Δ*::*natMX* strain and a strain expressing TAP-tagged Pdr1 as the sole Pdr1 source; ρ0 derivatives were generated by ethidium bromide treatment and confirmed by DAPI staining and inability to grow on nonfermentable carbon source.
  • ChIP-seq was performed with anti-Pdr1 and anti-TAP antibodies in ρ+ and ρ0 cells, with controls including *pdr1Δ* chromatin and no-primary-antibody reactions; libraries were sequenced on an Illumina HiSeq 2500 and reads aligned to the *C. glabrata* genome ASM254v2 with Bowtie 2.
  • Peaks were assessed with spp and ccQualityControl, annotated with ChipPeakAnno and annotatePeaks.pl, and motif discovery used MEME; selected promoters (*CDR1*, *YBT1*, *MEC3*, *PUP1*) were validated by standard ChIP-PCR.

Limitations

  • Stated: *PDR1* itself was not included in the 25-gene list because anti-Pdr1 ChIP-seq did not reproduce the anti-TAP signal at its promoter; the authors note possible epitope occlusion and state that further analyses are required to confirm Pdr1 binding to its own promoter.
  • Stated: two binding sites between divergently transcribed gene pairs were identified, but because those genes were not reported as ρ0-induced, the significance of their Pdr1 association remains to be determined.
  • Stated/evident: the authors emphasize that PDRE function requires direct functional validation, since sequence-based predictions can be misleading; most target promoters were not functionally tested, and the 25-gene set is described as a minimal list from a laboratory strain rather than clinical isolates.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1128/aac.03921-14

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 47 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The anti-TAP Western blotting detected a single species consistent with the predicted approximately 150-kDa size of the full-length TAP-Pdr1 fusion protein.

    “The anti-TAP Western blotting also detected a single species of protein immunoreactive with this antibody that was consistent with the predicted ∼150-kDa size of the full-length TAP-Pdr1 fusion protein.”
    Quote in the paperSubstantial claim
  • Findingown data

    Two other binding sites placed between divergently transcribed genes were identified, located between CAGL0B02101/CAGL0B02079 and CAGL0C02937g/CAGL0C02893g.

    “Two other binding sites placed between divergently transcribed genes were also identified. These elements were located between the CAGL0B02101/CAGL0B02079 and CAGL0C02937g/CAGL0C02893g genes.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The most abundant target gene directs production of membrane transporter proteins.

    “The most abundant target gene directs production of membrane transporter proteins.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Our analysis identified a set of 25 genes showing reproducible enrichment using the anti-Pdr1 antiserum in rho0 cells compared to rho+ cells.

    “Our analysis identified a set of 25 genes showing reproducible enrichment using the anti-Pdr1 antiserum in ρ0 cells compared to results in ρ+ cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    ChIP analysis showed increased representation of the CDR1, YBT1, MEC3, and PUP1 promoters in a ChIP sample from ρ0 cells compared to that from ρ+ cells.

    “As predicted by the ChIP-seq analysis, increased representation of all of these promoters is seen in a ChIP sample from ρ0 cells compared to that from ρ+ cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The anti-Pdr1 antiserum specifically immunoprecipitates Pdr1 in the ChIP assays.
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Findingown data

    A strong ChIP-seq signal was detected at the PDR1 promoter using the anti-TAP antibody, but this was not reproduced with the anti-Pdr1 antiserum.

    “While a strong ChIP-seq signal was detected using the anti-TAP antibody, we were not able to reproduce this with the anti-Pdr1 antiserum.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MEME analysis detected a site closely related to the S. cerevisiae PDRE and very similar to a site identified earlier in C. glabrata based on expression analyses.

    “This analysis detected a site ([Fig. 2B](#F2)) closely related to the *S. cerevisiae* PDRE that is also very similar to a site identified earlier in *C. glabrata* based on expression analyses ([11](#B11)).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11](#B11)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The proteins encoded by the Pdr1-regulated genes fit into roughly 7 different categories.

    “The proteins encoded by these genes fit into roughly 7 different categories.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    YIM1 is one of a divergently transcribed gene pair, with the DNA repair enzyme Mec3 encoded by the neighboring gene.

    “*YIM1* is one of a divergently transcribed gene pair, with the DNA repair enzyme Mec3 encoded by the neighboring gene.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Several other Pdr1 target genes are related at some level to metabolic functions but have additional recognized roles.

    “Several other Pdr1 target genes are related at some level to metabolic functions but have additional recognized roles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A gene encoding a second mitochondrial protein, called Yim1, was also induced in ρ0 cells and contained a likely PDRE in its promoter.

    “A gene encoding a second mitochondrial protein, called Yim1, was also induced in ρ0 cells and contained a likely PDRE in its promoter.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Both the YIM1 and MEC3 loci were induced in ρ0 cells.

    “Both of these loci were induced in ρ0 cells and seem likely to be coregulated by Pdr1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    NCE103 is a Pdr1-regulated gene involved in metabolism, encoding a carbonic anhydrase homologue.

    “The final Pdr1-regulated gene involved in metabolism is the *NCE103* gene, encoding a carbonic anhydrase homologue.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    CAGL0A01650g encodes a relatively acidic and small protein of 118 residues.

    “This gene encodes a relatively acidic and small protein of 118 residues.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The protein produced by the S. cerevisiae YGR346c gene shares no significant similarity with the C. glabrata protein.

    “However, the protein produced by this gene shares no significant similarity with the *C. glabrata* protein.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Using MEME to examine the DNA regions minimized bias in the analysis of C. glabrata promoters.

    “In order to minimize bias in our analysis of these *C. glabrata* promoters, we used the software tool MEME ([27](#B27)) to examine all of these DNA regions for common elements.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27](#B27)

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  • May combine two claims.

    Study design and conductown data

    The recombinant Pdr1 fragment was shown to bind DNA in a sequence-specific manner, indicating it was likely to fold correctly when produced in bacteria.

    “This fragment was shown to be able to bind DNA in a sequence-specific manner, indicating that it was likely to fold correctly when produced in bacteria, and was used to raise a polyclonal antiserum from rabbits.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premiseown data

    In that mutant derivative, the last two PDREs predicted from sequence considerations (TTCCACGGGA and CTCCACGGGA) would still be present, yet no ρ0 activation was seen.

    “However, in this mutant derivative, the last two PDREs predicted from sequence considerations (TTCCACGGGA and CTCCACGGGA) would still be present, yet we saw no ρ0 activation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15](#B15)

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Where replicate samples were found, an irreproducible discovery rate cutoff of 0.01 was used to establish significance threshold criteria.

    “Where replicate samples were found, an irreproducible discovery rate cutoff of 0.01 was used to establish significance threshold criteria; otherwise, significance was not determined, but further filtering was done by merging peaks called under different conditions, and the overlap between sets was used.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The TAP-tagged version of Pdr1 retains the normal function and regulation of wild-type Pdr1.

    “This comparison was taken as evidence that the TAP-tagged version of Pdr1 retains the normal function and regulation of wild-type Pdr1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The consensus PDRE in S. cerevisiae contains the core element TCCGCGGA and is found in the vast majority of genes under the control of the Pdr regulon.

    “The consensus PDRE in *S. cerevisiae* contains the core element TCCGCGGA and is found in the vast majority of genes under the control of the Pdr regulon (reviewed in references [24](#B24) to [26](#B26)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24](#B24)

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    • cites [26](#B26)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Standard single gene ChIP analysis was used to confirm the ChIP-seq data.

    “We used standard single gene ChIP analysis to confirm our ChIP-seq data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    ATF2 encodes a related enzyme that may also function in detoxification.

    “A related enzyme that may also function in detoxification is encoded by *ATF2*.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    These oxidoreductases are thought to contribute to drug resistance via detoxification or repair of macromolecules in the cell.

    “These oxidoreductases are thought to contribute to drug resistance via detoxification or repair of macromolecules in the cell ([36](#B36)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36](#B36)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Activation of the Pdr regulon has been argued to be involved in DNA repair in S. cerevisiae.

    “Activation of the Pdr regulon has been argued to be involved in DNA repair in *S. cerevisiae* ([52](#B52)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52](#B52)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Yim1 is also an oxidoreductase and may provide a mitochondrial equivalent of proteins like Ynl034c.

    “Yim1 is also an oxidoreductase and may provide a mitochondrial equivalent of proteins like Ynl034c, for example.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    S. cerevisiae has at least 4 other ABCC-class vacuolar ABC transporters, and there is essentially no data linking any of these with multidrug resistance in this organism.

    “While *S. cerevisiae* has at least 4 other ABCC-class vacuolar ABC transporters (reviewed in reference [32](#B32)), there is essentially no data linking any of these with multidrug resistance in this organism.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32](#B32)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Ipt1 directs synthesis of the final complex sphingolipid present in the plasma membrane, while Pdr16 is involved in lipid droplet mobilization and phosphoinositide signaling.

    “Ipt1 directs synthesis of the final complex sphingolipid present in the plasma membrane ([41](#B41)), while Pdr16 is involved in lipid droplet mobilization and phosphoinositide signaling ([42](#B42)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [41](#B41)

      Not checked in the free run.

    • cites [42](#B42)

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  • May combine two claims.

    Premisecitation

    NCE103 plays an essential role in growth in the presence of low CO2 levels; high CO2 levels support growth when NCE103 is deleted from C. glabrata, S. cerevisiae, or C. albicans.

    “This enzyme plays an essential role in growth in the presence of low CO2 levels; high CO2 levels support growth when *NCE103* is deleted from *C. glabrata* ([37](#B37)), as well as *S. cerevisiae* ([38](#B38)) or *C. albicans* ([39](#B39)).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [37](#B37)

      Not checked in the free run.

    • cites [38](#B38)

      Not checked in the free run.

    • cites [39](#B39)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Two oxidoreductases, encoded by YMR102c and YNL134c, were found to be regulated by either Yrr1 or Pdr1 in S. cerevisiae and implicated as part of the Pdr regulon in this organism.

    “Two of these oxidoreductases, encoded by *YMR102c* and *YNL134c*, were found to be regulated by either Yrr1 or Pdr1 in *S. cerevisiae* and implicated as part of the Pdr regulon in this organism ([34](#B34), [35](#B35)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34](#B34)

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    • cites [35](#B35)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Both IPT1 and PDR16 were previously shown to be under the control of the Pdr regulon in S. cerevisiae.

    “Both of these genes were previously shown to be under the control of the Pdr regulon in *S. cerevisiae* ([43](#B43), [44](#B44)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [43](#B43)

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    • cites [44](#B44)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ATF2 is outside the S. cerevisiae Pdr regulon and plays an important role in modification of alkyl compounds to ester derivatives.

    “This gene is also outside the *S. cerevisiae* Pdr regulon and plays an important role in modification of alkyl compounds to ester derivatives ([37](#B37)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37](#B37)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bag7 controls the activity of the Rho1 GTPase in S. cerevisiae in a manner distinct from that of its close relative Sac7.

    “Bag7 controls the activity of the Rho1 GTPase in *S. cerevisiae* in a manner distinct from that of its close relative Sac7 ([49](#B49)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49](#B49)

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  • May combine two claims.

    Premisecitation

    Overproduction of Pup1 and Cdr1 was sufficient to partially reproduce the phenotypes of clinical isolates containing GOF forms of Pdr1, consistent with the idea that these two genes are major contributors to the downstream effects of Pdr1 genetic activation.

    “Overproduction of Pup1 and Cdr1 was sufficient to partially reproduce the phenotypes of clinical isolates containing GOF forms of Pdr1, consistent with the idea that these two genes are major contributors to the downstream effects of Pdr1 genetic activation ([50](#B50)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50](#B50)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    These membrane proteins are overproduced in azole-resistant C. glabrata, C. albicans, and S. cerevisiae.

    “These membrane proteins are overproduced in azole-resistant *C. glabrata*, *C. albicans*, and *S. cerevisiae* ([12](#B12), [45](#B45), [46](#B46)).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [12](#B12)

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    • cites [45](#B45)

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    • cites [46](#B46)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Evidence exists that these 7-TM proteins can control internalization of both membrane proteins and sphingolipid intermediates at the level of the plasma membrane.

    “Their precise biological function is somewhat controversial, but evidence exists that these 7-TM proteins can control internalization of both membrane proteins and sphingolipid intermediates at the level of the plasma membrane ([47](#B47), [48](#B48)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [47](#B47)

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    • cites [48](#B48)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    REV1 encodes a DNA polymerase important in translesion repair.

    “which encodes a DNA polymerase important in translesion repair (reviewed in reference [51](#B51))”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51](#B51)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PUP1 was previously identified as a strong and commonly induced gene in clinical isolates, although its function is unknown.

    “*PUP1* was previously identified as a strong and commonly induced gene in clinical isolates ([50](#B50)), although its function is unknown.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50](#B50)

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Ybt1 is localized to the vacuolar membrane-localized ABCC ABC transporter that has been implicated in phosphatidylcholine metabolism in S. cerevisiae.

    “Ybt1 is localized to the vacuolar membrane-localized ABCC ABC transporter that has been implicated in phosphatidylcholine metabolism in *S. cerevisiae* ([30](#B30), [31](#B31)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30](#B30)

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    • cites [31](#B31)

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  • Classified as probably not a substantial claim.

    Premisecitation

    CO2 sensing regulates virulence in C. albicans and Cryptococcus neoformans.

    “CO2 sensing regulates virulence in *C. albicans* ([39](#B39)) and *Cryptococcus neoformans* ([40](#B40))”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39](#B39)

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    • cites [40](#B40)

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    Premisecitation

    An ABCC transporter required for normal virulence is found in the vacuole of the major fungal pathogen Candida albicans.

    “Strikingly, an ABCC transporter required for normal virulence is found in the vacuole of the major fungal pathogen *Candida albicans* ([33](#B33)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33](#B33)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    HAP1 encodes a zinc finger-containing transcription factor that can function as an activator protein under aerobic conditions and a repressor in the absence of oxygen.

    “*HAP1* encodes a zinc finger-containing transcription factor that can function as an activator protein under aerobic conditions and a repressor in the absence of oxygen ([54](#B54)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54](#B54)

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  • May combine two claims.

    Interpretationown data

    C. glabrata Pdr1 binds upstream of and regulates novel genes that show no evidence for coordinate transcriptional control in S. cerevisiae.

    “While in broad strokes (increased expression of ABC transporters, membrane biosynthetic enzymes, and metabolic enzymes) these responses are similar, *C. glabrata* Pdr1 binds upstream of and regulates novel genes that show no evidence for coordinate transcriptional control in *S. cerevisiae*.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    CAGL0A01650g is 12-fold induced in ρ0 cells, making it one of the top 5 genes responding to this regulatory signal.

    “This gene, called *CAGL0A01650g*, is 12-fold induced in ρ0 cells, making it one of the top 5 genes responding to this regulatory signal ([14](#B14)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14](#B14)

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  • May combine two claims.

    Interpretationreasoning

    These transcription factors can amplify the range of genes that are regulated by Pdr1 and may help explain the larger list of genes exhibiting stimulated expression in strains containing GOF alleles of PDR1.

    “These transcription factors can amplify the range of genes that are regulated by Pdr1 and may help explain the larger list of genes exhibiting stimulated expression in strains containing GOF alleles of *PDR1* ([7](#B7), [10](#B10)[–](#B11)[12](#B12)).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7](#B7)

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    • cites [10](#B10)

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    • cites [12](#B12)

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40 of 40

  • The paper relies on this without support.

    Existing transcriptome analyses cannot separate direct from indirect Pdr1 target genes.

    “While extensive analyses of the transcriptional effects of Pdr1 have identified a number of genes that are regulated by this factor, we cannot yet separate direct from indirect target genes.”
    “While the picture of the Pdr1-responsive transcriptome is well developed, we know very little about the direct targets of this transcription factor.”

  • The paper relies on this without support.

    The anti-Pdr1 antiserum specifically immunoprecipitates Pdr1 in the ChIP assays.

    “In all cases, the anti-Pdr1 antiserum was used as the immunoprecipitating antibody.”

  • The paper relies on this without support.

    Oye2 and Yir036c have not been associated with Pdr regulation in S. cerevisiae.

    “The remaining enzymes, Oye2 and Yir036c, have not been associated with Pdr regulation in *S. cerevisiae* and may represent new acquisitions for the *C. glabrata* Pdr regulon.”
3 of 3

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Authors
Paul, S., Bair, T. B., & Moye-Rowley, W. S.
Affiliations
  • University of Iowa (US)
  • Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa USA
ORCID
Paul, Sanjoy
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2014-11
Volume
58
Issue
11
Pages
6904-6912
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.03921-14
PMC
PMC4249425
OpenAlex
W2168210645
Semantic Scholar
8f5c8a797d6ca2b348c208ac5d26bd7ab186a258
Cited by
45
References
56
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 3
FWCI
2.33
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM049825, GM49825)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords
Candida glabrata, azole resistance, DNA repair genes, transcriptional regulation, promoter identification, ChIP-seq
MeSH terms
Antifungal Agents, Base Sequence, Binding Sites, Candidiasis, DNA-Binding Proteins, Fungal Proteins, Mitochondria, Transcription Factors, Fluconazole, Sequence Analysis, DNA, ATP-Binding Cassette Transporters, Drug Resistance, Fungal, Candida glabrata, High-Throughput Nucleotide Sequencing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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