scholarly journals Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors

2008 ◽  
Vol 7 (7) ◽  
pp. 1168-1179 ◽  
Author(s):  
Yong-Un Baek ◽  
Mingchun Li ◽  
Dana A. Davis
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Iron Acquisition ◽  
Mammalian Host ◽  
Regulatory Sequence ◽  
Ferric Reductase ◽  
Reductase Gene ◽  
Ferric Reductases

ABSTRACT Iron is an essential nutrient that is severely limited in the mammalian host. Candida albicans encodes a family of 15 putative ferric reductases, which are required for iron acquisition and utilization. Despite the central role of ferric reductases in iron acquisition and mobilization, relatively little is known about the regulatory networks that govern ferric reductase gene expression in C. albicans. Here we have demonstrated the differential regulation of two ferric reductases, FRE2 and FRP1, in response to distinct iron-limited environments. FRE2 and FRP1 are both induced in alkaline-pH environments directly by the Rim101 transcription factor. However, FRP1 but not FRE2 is also induced by iron chelation. We have identified a CCAAT motif as the critical regulatory sequence for chelator-mediated induction and have found that the CCAAT binding factor (CBF) is essential for FRP1 expression in iron-limited environments. We found that a hap5Δ/hap5Δ mutant, which disrupts the core DNA binding activity of CBF, is unable to grow under iron-limited conditions. C. albicans encodes three CBF-dependent transcription factors, and we identified the Hap43 protein as the CBF-dependent transcription factor required for iron-limited responses. These studies provide key insights into the regulation of ferric reductase gene expression in the fungal pathogen C. albicans.

scholarly journals Regulation of EphA8 Gene Expression by TALE Homeobox Transcription Factors during Development of the Mesencephalon

2006 ◽  
Vol 27 (5) ◽  
pp. 1614-1630 ◽  
Author(s):  
Sungbo Shim ◽  
Yujin Kim ◽  
Jongdae Shin ◽  
Jieun Kim ◽  
Soochul Park
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Regulatory Region ◽  
Dominant Negative ◽  
Regulatory Sequence ◽  
Enhancer Activity ◽  
Homeobox Transcription Factor ◽  
Homeobox Transcription Factors

ABSTRACT The mouse ephA8 gene is expressed in a rostral-to-caudal gradient in the developing superior colliculus, and these EphA gradients may contribute to the proper development of the retinocollicular projection. Thus, it is of considerable interest to elucidate how the ephA8 gene expression is controlled by upstream regulators during the development of the mesencephalon. In this study, we employed in vivo expression analysis in transgenic mouse embryos to dissect the cis-acting DNA regulatory region, leading to the identification of a CGGTCA sequence critical for the ephA8 enhancer activity. Using this element as the target in a yeast one-hybrid system, we identified a Meis homeobox transcription factor. Significantly, DNA binding sites for Pbx, another TALE homeobox transcription factor, were also identified in the ephA8 enhancer region. Meis2 and Pbx1/2 are specifically expressed in the entire region of the dorsal mesencephalon, where specific colocalization of EphA8 and Meis is restricted to a subset of cells. Meis2 and Pbx2 synergistically bind the ephA8 regulatory sequence in vitro, and this interaction is critical for the transcriptional activation of a reporter construct bearing the ephA8 regulatory region in the presence of histone deacetylase inhibitor. More importantly, when expressed in the embryonic midbrain, the dominant-negative form of Meis down-regulates endogenous ephA8. Interestingly, we found that both Meis2 and Pbx2 are constitutively bound in the ephA8 regulatory region in the dorsal mesencephalon. These studies strongly suggest that Meis and Pbx homeobox transcription factors tightly associate with the ephA8 regulatory sequence and require an additional unidentified regulator to ensure the specific activation of ephA8.

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Wild Type ◽  
Elevated Expression ◽  
Factor C ◽  
Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

scholarly journals Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

2021 ◽  
Vol 15 ◽  
Author(s):  
Ana Belén Iglesias González ◽  
Jon E. T. Jakobsson ◽  
Jennifer Vieillard ◽  
Malin C. Lagerström ◽  
Klas Kullander ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Axon Guidance ◽  
Single Cell ◽  
Cellular Activity ◽  
Electrophysiological Properties ◽  
Related Transcription Factor ◽  
Unique Markers ◽  
Molecular Code

The spinal locomotor network is frequently used for studies into how neuronal circuits are formed and how cellular activity shape behavioral patterns. A population of dI6 interneurons, marked by the Doublesex and mab-3 related transcription factor 3 (Dmrt3), has been shown to participate in the coordination of locomotion and gaits in horses, mice and zebrafish. Analyses of Dmrt3 neurons based on morphology, functionality and the expression of transcription factors have identified different subtypes. Here we analyzed the transcriptomes of individual cells belonging to the Dmrt3 lineage from zebrafish and mice to unravel the molecular code that underlies their subfunctionalization. Indeed, clustering of Dmrt3 neurons based on their gene expression verified known subtypes and revealed novel populations expressing unique markers. Differences in birth order, differential expression of axon guidance genes, neurotransmitters, and their receptors, as well as genes affecting electrophysiological properties, were identified as factors likely underlying diversity. In addition, the comparison between fish and mice populations offers insights into the evolutionary driven subspecialization concomitant with the emergence of limbed locomotion.

scholarly journals Effect of Environmental pH on Morphological Development of Candida albicans Is Mediated via the PacC-Related Transcription Factor Encoded by PRR2

1999 ◽  
Vol 181 (24) ◽  
pp. 7524-7530 ◽  
Author(s):  
Ana M. Ramon ◽  
Amalia Porta ◽  
William A. Fonzi
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Feedback Loop ◽  
Response Regulator ◽  
Morphological Development ◽  
Alkaline Ph ◽  
Ph Response ◽  
Related Transcription Factor ◽  
Ph Dependent

ABSTRACT The ability to respond to ambient pH is critical to the growth and virulence of the fungal pathogen Candida albicans. This response entails the differential expression of several genes affecting morphogenesis. To investigate the mechanism of pH-dependent gene expression, the C. albicans homolog of pacC, designated PRR2 (for pH response regulator), was identified and cloned. pacC encodes a zinc finger-containing transcription factor that mediates pH-dependent gene expression inAspergillus nidulans. Mutants lacking PRR2 can no longer induce the expression of alkaline-expressed genes or repress acid-expressed genes at alkaline pH. Although the mutation did not affect growth of the cells at acid or alkaline pH, the mutants exhibited medium-conditional defects in filamentation. PRR2was itself expressed in a pH-conditional manner, and its induction at alkaline pH was controlled by PRR1. PRR1 is homologous to palF, a regulator of pacC. Thus,PRR2 expression is controlled by a pH-dependent feedback loop. The results demonstrate that the pH response pathway ofAspergillus is conserved and that this pathway has been adapted to control dimorphism in C. albicans.

scholarly journals Tec1p-Independent Activation of a Hypha-Associated Candida albicans Virulence Gene during Infection

2004 ◽  
Vol 72 (4) ◽  
pp. 2386-2389 ◽  
Author(s):  
Peter Staib ◽  
Ayfer Binder ◽  
Marianne Kretschmar ◽  
Thomas Nichterlein ◽  
Klaus Schröppel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Animal Models ◽  
Environmental Conditions ◽  
Deletion Mutant ◽  
Virulence Gene ◽  
Consensus Sequences ◽  
Site Consensus

ABSTRACT The Tec1p transcription factor is involved in the expression of hypha-specific genes in Candida albicans. Although the induction of the hypha-associated SAP5 gene by serum in vitro depends on Tec1p, deletion of all Tec1p binding site consensus sequences from the SAP5 promoter did not affect its activation. In two different animal models of candidiasis, the SAP5 promoter was induced even in a Δtec1 deletion mutant, demonstrating that the requirement for Tec1p in gene expression in C. albicans depends on the environmental conditions within the host.

scholarly journals The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

1994 ◽  
Vol 14 (11) ◽  
pp. 7517-7526 ◽  
Author(s):  
H S Ip ◽  
D B Wilson ◽  
M Heikinheimo ◽  
Z Tang ◽  
C N Ting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cardiac Muscle ◽  
Binding Site ◽  
Cardiac Myocytes ◽  
Specific Binding ◽  
Troponin C ◽  
Specific Gene ◽  
Cardiac Muscle Cells

The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.

Induction of Bach1 and ARA70 gene expression at an early stage of adipocyte differentiation of mouse 3T3-L1 cells

2002 ◽  
Vol 361 (3) ◽  
pp. 629-633 ◽  
Author(s):  
Makoto NISHIZUKA ◽  
Tomoko TSUCHIYA ◽  
Tsutomu NISHIHARA ◽  
Masayoshi IMAGAWA
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
3T3 Cells ◽  
Subtraction Method ◽  
Proliferating Cells ◽  
Genes Encoding ◽  
Nih 3T3

Using a subtraction method, we have isolated genes that are induced early in the differentiation of mouse 3T3-L1 preadipocyte cells into adipocytes. These include the genes encoding transcription factors and signalling proteins, as well as unknown genes. Bach1, a transcription factor, and ARA70, a cofactor, were rapidly induced during differentiation. The induction of these two genes was observed only in growth-arrested 3T3-L1 cells, and not in proliferating cells. In NIH-3T3 cells, no induction was observed under either set of conditions. These results strongly indicate that Bach1 and ARA70 have valuable roles at the onset of adipocyte differentiation.

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