Gene regulation in the white–opaque transition ofCandida albicans

1995 ◽  
Vol 73 (S1) ◽  
pp. 1049-1057 ◽  
Author(s):  
David R. Soll ◽  
Thyagarajan Srikantha ◽  
Brian Morrow ◽  
Anand Chandrasekhar ◽  
Klaus Schröppel ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Phenotypic Switching ◽  
Upstream Region ◽  
Specific Gene ◽  
Regulatory Sequences ◽  
Promoter Regions ◽  
Coordinate Regulation ◽  
Cis Acting ◽  
Ofcandida Albicans ◽  
Differential Transcription

Most strains of Candida albicans switch frequently and reversibly among a number of different phenotypes distinguishable by colony morphology. Previous experiments indicated that switching involved differential gene expression. Using the white–opaque transition as a model switching system, we have cloned two opaque-specific genes, PEP1 and OP4, and one white specific gene, WH11. Differential transcription of these genes suggested that switching involves the coordinate regulation of batteries of unlinked phase-specific genes. It has been demonstrated that the frequency of integration at phase specific loci is a function of the transcriptional state of the phase-specific genes. In addition, a functional dissection of the 5′-upstream region of the WH11 gene has identified two major domains containing cis-acting regulatory sequences that are involved in phase-specific transcription. Gel retardation experiments provide evidence for white phase-specific trans-acting factors which form complexes with both domains. The regulation of the switching event is discussed. Key words: Candida albicans, phenotypic switching, white–opaque transition, phase-specific genes, integrative transformation, promoter regions, WH11 gene.

scholarly journals Cis-regulatory variants affect gene expression dynamics in yeast

2021 ◽  
Author(s):  
Ching-Hua Shih ◽  
Justin C. Fay
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Regulatory Sequences ◽  
Diauxic Shift ◽  
Promoter Regions ◽  
Specific Expression ◽  
Cis Acting ◽  
Regulatory Variants ◽  
Endogenous Expression ◽  
Gene Expression Dynamics

Evolution of cis-regulatory sequences depends on how they effect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-acting variation in gene expression dynamics. Within species ASE is associated with intergenic variants, but ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression we identified and characterized cis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in cis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects expression are relevant to the evolution of cis-regulatory sequences.

Multiple hormone-inducible enhancers as mediators of differential transcription

1986 ◽  
Vol 6 (12) ◽  
pp. 4526-4538
Author(s):  
M G Toohey ◽  
K L Morley ◽  
D O Peterson
Keyword(s):  
Regulatory Control ◽  
Regulatory Sequences ◽  
Enhancer Element ◽  
Cis Acting ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Differential Transcription ◽  
Virus Promoter ◽  
Inducible Gene

Sets of genes under a common regulatory control in a given cell type are often differentially transcribed. The possibility that this differential transcription can be modulated by the number or strength of cis-acting regulatory sequences associated with a given gene was tested by using the glucocorticoid-responsive enhancer element associated with the mouse mammary tumor virus promoter. Results indicate that differential levels of hormone-inducible gene expression can be modulated in an additive way by the number of glucocorticoid-responsive enhancers associated with this promoter. Realization of these effects shows little preference for position of the additional elements with respect to the promoter. When sequences that bind the glucocorticoid receptor in vitro with somewhat lower affinity than the enhancer were tested, these additive effects were not detected. The results support that differential transcription of genes subject to a common regulatory control can be mediated, at least in part, by the number or strength of their associated cis-acting regulatory sequences.

scholarly journals Multiple hormone-inducible enhancers as mediators of differential transcription.

1986 ◽  
Vol 6 (12) ◽  
pp. 4526-4538 ◽  
Author(s):  
M G Toohey ◽  
K L Morley ◽  
D O Peterson
Keyword(s):  
Regulatory Control ◽  
Regulatory Sequences ◽  
Enhancer Element ◽  
Cis Acting ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Differential Transcription ◽  
Virus Promoter ◽  
Inducible Gene

Sets of genes under a common regulatory control in a given cell type are often differentially transcribed. The possibility that this differential transcription can be modulated by the number or strength of cis-acting regulatory sequences associated with a given gene was tested by using the glucocorticoid-responsive enhancer element associated with the mouse mammary tumor virus promoter. Results indicate that differential levels of hormone-inducible gene expression can be modulated in an additive way by the number of glucocorticoid-responsive enhancers associated with this promoter. Realization of these effects shows little preference for position of the additional elements with respect to the promoter. When sequences that bind the glucocorticoid receptor in vitro with somewhat lower affinity than the enhancer were tested, these additive effects were not detected. The results support that differential transcription of genes subject to a common regulatory control can be mediated, at least in part, by the number or strength of their associated cis-acting regulatory sequences.

scholarly journals Comparative genomics of white and opaque cell states supports an epigenetic mechanism of phenotypic switching in Candida albicans

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Chapman N Beekman ◽  
Christina A Cuomo ◽  
Richard J Bennett ◽  
Iuliana V Ene
Keyword(s):  
Candida Albicans ◽  
Candida Species ◽  
Control Cell ◽  
Epigenetic Mechanism ◽  
Phenotypic Switching ◽  
Transcriptional Networks ◽  
Specific Gene ◽  
Epigenetic Mechanisms ◽  
Genetic Changes ◽  
Physiological Properties

Abstract Several Candida species can undergo a heritable and reversible transition from a ‘white’ state to a mating proficient ‘opaque’ state. This ability relies on highly interconnected transcriptional networks that control cell-type-specific gene expression programs over multiple generations. Candida albicans, the most prominent pathogenic Candida species, provides a well-studied paradigm for the white-opaque transition. In this species, a network of at least eight transcriptional regulators controls the balance between white and opaque states that have distinct morphologies, transcriptional profiles, and physiological properties. Given the reversible nature and the high frequency of white-opaque transitions, it is widely assumed that this switch is governed by epigenetic mechanisms that occur independently of any changes in DNA sequence. However, a direct genomic comparison between white and opaque cells has yet to be performed. Here, we present a whole-genome comparative analysis of C. albicans white and opaque cells. This analysis revealed rare genetic changes between cell states, none of which are linked to white-opaque switching. This result is consistent with epigenetic mechanisms controlling cell state differentiation in C. albicans and provides direct evidence against a role for genetic variation in mediating the switch.

scholarly journals Genome-Wide Analysis of Major Facilitator Superfamily and Its Expression in Response of Poplar to Fusarium oxysporum

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Diao ◽  
Shuxuan Li ◽  
Ling Ma ◽  
Ping Zhang ◽  
Jianyang Bai ◽  
...  
Keyword(s):  
Fusarium Oxysporum ◽  
Populus Trichocarpa ◽  
Major Facilitator Superfamily ◽  
Specific Gene ◽  
Promoter Regions ◽  
Cis Acting ◽  
Protein Motifs ◽  
Duplication Events ◽  
Gene Structures ◽  
Major Facilitator

The major facilitator superfamily (MFS) is one of the largest known membrane transporter families. MFSs are involved in many essential functions, but studies on the MFS family in poplar have not yet been reported. Here, we identified 41 MFS genes from Populus trichocarpa (PtrMFSs). We built a phylogenetic tree, which clearly divided members of PtrMFS into six groups with specific gene structures and protein motifs/domains. The promoter regions contain various cis-acting elements involved in stress and hormone responsiveness. Genes derived from segmental duplication events are unevenly distributed in 17 poplar chromosomes. Collinearity analysis showed that PtrMFS genes are conserved and homologous to corresponding genes from four other species. Transcriptome data indicated that 40 poplar MFS genes were differentially expressed when treated with Fusarium oxysporum. Co-expression networks and gene function annotations of MFS genes showed that MFS genes tightly co-regulated and closely related in function of transmembrane transport. Taken together, we systematically analyzed structure and function of genes and proteins in the PtrMFS family. Evidence indicated that poplar MFS genes play key roles in plant development and response to a biological stressor.

scholarly journals A GBF-binding site and a novel AT element define the minimal sequences sufficient to direct prespore-specific expression in Dictyostelium discoideum.

1994 ◽  
Vol 14 (9) ◽  
pp. 5840-5849 ◽  
Author(s):  
J A Powell-Coffman ◽  
G R Schnitzler ◽  
R A Firtel
Keyword(s):  
Dictyostelium Discoideum ◽  
Molecular Mechanisms ◽  
Gene Activation ◽  
Point Mutations ◽  
Specific Gene ◽  
Regulatory Sequences ◽  
Specific Expression ◽  
Cis Acting ◽  
Minimal Sequences

In order to better understand the molecular mechanisms of cellular differentiation in Dictyostelium discoideum, we have identified the minimum regulatory sequences of the prespore-specific gene SP60/cotC that are sufficient to confer cell-type-specific expression on a heterologous promoter. This region includes at least two essential cis-acting elements: a novel AT-rich element (or elements) and CAE3. The essential function of the AT element is confirmed through point mutations that decrease expression below the level of detection. CAE3 is one of three CA-rich elements (CAEs) required for the induction of SP60/cotC during development or in response to extracellular cyclic AMP. The CAEs have differential affinities for a specific developmentally induced nuclear activity (CAE1 > CAE2 >> CAE3). Here, we identify this activity as G-box-binding factor (GBF) and show that in vitro-transcribed and -translated GBF binds all three SP60/cotC CAEs in a sequence-specific manner. Previous studies have suggested that GBF mediates the induction of some prestalk genes, and these results demonstrate that it also has a specific role in prespore gene activation.

scholarly journals Global Roles of Ssn6 in Tup1- and Nrg1-dependent Gene Regulation in the Fungal Pathogen,Candida albicans

2005 ◽  
Vol 16 (6) ◽  
pp. 2913-2925 ◽  
Author(s):  
Susana García-Sánchez ◽  
Abigail L. Mavor ◽  
Claire L. Russell ◽  
Silvia Argimon ◽  
Paul Dennison ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Budding Yeast ◽  
Pathogenic Fungus ◽  
Phenotypic Switching ◽  
Specific Gene ◽  
Cellular Morphogenesis ◽  
Number Of Genes

In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast.

scholarly journals Functional analysis of the promoter of the phase-specific WH11 gene of Candida albicans.

1995 ◽  
Vol 15 (3) ◽  
pp. 1797-1805 ◽  
Author(s):  
T Srikantha ◽  
A Chandrasekhar ◽  
D R Soll
Keyword(s):  
Candida Albicans ◽  
Firefly Luciferase ◽  
Upstream Region ◽  
Protein Extract ◽  
Cis Acting ◽  
Activation Domains ◽  
White Phase ◽  
Phase Protein ◽  
Specific Complex ◽  
The Individual

Candida albicans WO-1 switches spontaneously, frequently, and reversibly between a hemispherical white and a flat gray (opaque) colony-forming phenotype. This transition affects a number of morphological and physiological parameters and involves the activation and deactivation of phase-specific genes. The WH11 gene is transcribed in the white but not the opaque phase. A chimeric WH11-firefly luciferase gene containing the 5' upstream region of WH11 was demonstrated to be under phase regulation regardless of the site of integration, and a series of promoter deletion constructs was used to delineate two white-phase-specific transcription activation domains. Gel retardation experiments with the individual distal or proximal domain and white-phase or opaque-phase protein extract demonstrated the formation of one distal white-phase-specific complex and two proximal white-phase-specific complexes. Specific subfragments were tested for their ability to compete with the entire domain in the formation of complexes with white-phase protein extract in order to map the proximal domain sequence involved in white-phase-specific complex formation. Our results indicate that white-phase-specific transcription of WH11 is positively regulated by trans-acting factors interacting with two cis-acting activation sequences in the WH11 promoter.

scholarly journals The Histone Deacetylase Genes HDA1 andRPD3 Play Distinct Roles in Regulation of High-Frequency Phenotypic Switching in Candida albicans

2001 ◽  
Vol 183 (15) ◽  
pp. 4614-4625 ◽  
Author(s):  
T. Srikantha ◽  
L. Tsai ◽  
K. Daniels ◽  
A. J. S. Klar ◽  
D. R. Soll
Keyword(s):  
Candida Albicans ◽  
Histone Deacetylase ◽  
High Frequency ◽  
Protein Gene ◽  
Phenotypic Switching ◽  
Specific Gene ◽  
Slight Reduction ◽  
Specific Expression ◽  
White Phase ◽  
High Level

ABSTRACT Five histone deacetylase genes (HDA1, RPD3, HOS1, HOS2, and HOS3) have been cloned fromCandida albicans and characterized. Sequence analysis and comparison with 17 additional deacetylases resulted in a phylogenetic tree composed of three major groups. Transcription of the deacetylases HDA1 and RPD3 is down-regulated in the opaque phase of the white-opaque transition in strain WO-1. HOS3 is selectively transcribed as a 2.5-kb transcript in the white phase and as a less-abundant 2.3-kb transcript in the opaque phase. HDA1 andRPD3 were independently deleted in strain WO-1, and both switching between the white and opaque phases and the downstream regulation of phase-specific genes were analyzed. Deletion ofHDA1 resulted in an increase in the frequency of switching from the white phase to the opaque phase, but had no effect on the frequency of switching from the opaque phase to the white phase. Deletion of RPD3 resulted in an increase in the frequency of switching in both directions. Deletion ofHDA1 resulted in reduced white-phase-specific expression of the EFG1 3.2-kb transcript, but had no significant effect on white-phase-specific expression of WH11 or opaque-phase-specific expression of OP4, SAP1, andSAP3. Deletion of RPD3 resulted in reduced opaque-phase-specific expression of OP4, SAP1, and SAP3 and a slight reduction of white-phase-specific expression of WH11 and 3.2-kbEFG1. Deletion of neither HDA1 norRPD3 affected the high level of white-phase expression and the low level of opaque-phase expression of the MADS box protein gene MCM1, which has been implicated in the regulation of opaque-phase-specific gene expression. In addition, there was no effect on the phase-regulated levels of expression of the other deacetylase genes. These results demonstrate that the two deacetylase genes HDA1 and RPD3 play distinct roles in the suppression of switching, that the two play distinct and selective roles in the regulation of phase-specific genes, and that the deacetylases are in turn regulated by switching.

scholarly journals Cloning and characterization of the human osteopontin gene and its promoter

1994 ◽  
Vol 303 (1) ◽  
pp. 255-262 ◽  
Author(s):  
N Hijiya ◽  
M Setoguchi ◽  
K Matsuura ◽  
Y Higuchi ◽  
S Akizuki ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Mouse Gene ◽  
Upstream Region ◽  
Regulatory Sequences ◽  
Major Band ◽  
Cis Acting ◽  
Consensus Sequences ◽  
Shift Analysis ◽  
Intron Structure ◽  
The Difference

We isolated the human osteopontin (hOP) gene and the 5′ upstream region, and analysed its exon-intron structure and potential regulatory sequences of the promoter region in comparison with those of the mouse and porcine gene. The coding sequence is split into 7 exons which are similar to those of the mouse gene, although the hOP gene is longer than the mouse gene. The difference in length is mainly due to variations in intron 3, which is approximately 2.7-fold longer than that of the mouse OP gene. The 5′ upstream region of the hOP, which is highly conserved up to nucleotide -250, contains a number of potential cis regulatory consensus sequences. A series of sequentially 5′-deleted chimeric clones was tested for the ability to stimulate chloramphenicol acetyltransferase (CAT). Initial CAT analysis demonstrated that nucleotides at positions -474 to -270, -124 to -80, and -55 to -39 contained cis-acting enhancing sequences in a human monocyte cell line, SCC-3, although the -124 to -80 region was much more active than other regions. Deletion of the sequences between -474 and -270 localized this cis region to the sequence at positions -439 to -410, whereas the deletion between -124 to -80 localized the regions to -124 to -115, and -94 to -80. Gel-shift analysis using as probes synthesized double-stranded DNA corresponding to the 10 and 15 bp region at positions -124 to -115 and -94 to -80 respectively revealed that each probe formed a major band complexed with nuclear proteins prepared from SCC-3 cells.

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