Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor

Effector-dependent manipulation of host transcription is a key virulence mechanism used by Xanthomonas species causing bacterial spot disease in tomato and pepper. Transcription activator-like (TAL) effectors employ novel DNA-binding domains to directly activate host transcription, whereas the non-TAL effector XopD uses a small ubiquitin-like modifier (SUMO) protease activity to represses host transcription. The targets of TAL and non-TAL effectors provide insight to the genes governing susceptibility and resistance during Xanthomonas infection. In this study, we investigated the extent to which the X. euvesicatoria non-TAL effector strain Xe85-10 activates tomato transcription to gain new insight to the transcriptional circuits and virulence mechanisms associated with Xanthomonas euvesicatoria pathogenesis. Using transcriptional profiling, we identified a putative basic helix-loop-helix (bHLH) transcription factor, bHLH132, as a pathogen-responsive gene that is moderately induced by microbe-associated molecular patterns and defense hormones and is highly induced by XopD during X. euvesicatoria infection. We also found that activation of bHLH132 transcription requires the XopD SUMO protease activity. Silencing bHLH132 mRNA expression results in stunted tomato plants with enhanced susceptibility to X. euvesicatoria infection. Our work suggests that bHLH132 is required for normal vegetative growth and development as well as resistance to X. euvesicatoria. It also suggests new transcription-based models describing XopD virulence and recognition in tomato.

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Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung

PLoS Pathogens ◽

10.1371/journal.ppat.1009235 ◽

2021 ◽

Vol 17 (3) ◽

pp. e1009235

Author(s):

Hong Liu ◽

Wenjie Xu ◽

Vincent M. Bruno ◽

Quynh T. Phan ◽

Norma V. Solis ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Aspergillus Fumigatus ◽

Transcriptional Profiling ◽

Transcriptional Response ◽

Gene Clusters ◽

Transcription Factor Genes ◽

And Function

To gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which is required for the organism to achieve maximal fungal burden in the lung. The other was sltA, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the ΔsltA mutant is due in part to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.

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Transcriptional Profiling ofSaccharomyces cerevisiaeReveals the Impact of Variation of a Single Transcription Factor on Differential Gene Expression in 4NQO, Fermentable, and Nonfermentable Carbon Sources

G3 Genes|Genome|Genetics ◽

10.1534/g3.117.300138 ◽

2017 ◽

Vol 8 (2) ◽

pp. 607-619 ◽

Cited By ~ 8

Author(s):

Xiaoqing Rong-Mullins ◽

Michael C. Ayers ◽

Mahmoud Summers ◽

Jennifer E. G. Gallagher

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Differential Gene Expression ◽

Transcriptional Profiling ◽

Carbon Sources ◽

Differential Gene ◽

The Impact

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Mutation in FBXO32 causes dilated cardiomyopathy through up-regulation of ER-stress mediated apoptosis

Communications Biology ◽

10.1038/s42003-021-02391-9 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Nadya Al-Yacoub ◽

Dilek Colak ◽

Salma Awad Mahmoud ◽

Maya Hammonds ◽

Kunhi Muhammed ◽

...

Keyword(s):

Transcription Factor ◽

Er Stress ◽

Target Genes ◽

Transcriptional Profiling ◽

Underlying Mechanism ◽

Effector Proteins ◽

Homozygous Mutation ◽

Unfolded Protein ◽

Canonical Pathways ◽

The Unfolded Protein Response

AbstractEndoplasmic reticulum (ER) stress induction of cell death is implicated in cardiovascular diseases. Sustained activation of ER-stress induces the unfolded protein response (UPR) pathways, which in turn activate three major effector proteins. We previously reported a missense homozygous mutation in FBXO32 (MAFbx, Atrogin-1) causing advanced heart failure by impairing autophagy. In the present study, we performed transcriptional profiling and biochemical assays, which unexpectedly revealed a reduced activation of UPR effectors in patient mutant hearts, while a strong up-regulation of the CHOP transcription factor and of its target genes are observed. Expression of mutant FBXO32 in cells is sufficient to induce CHOP-associated apoptosis, to increase the ATF2 transcription factor and to impair ATF2 ubiquitination. ATF2 protein interacts with FBXO32 in the human heart and its expression is especially high in FBXO32 mutant hearts. These findings provide a new underlying mechanism for FBXO32-mediated cardiomyopathy, implicating abnormal activation of CHOP. These results suggest alternative non-canonical pathways of CHOP activation that could be considered to develop new therapeutic targets for the treatment of FBXO32-associated DCM.

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Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung

10.1101/2020.12.23.424128 ◽

2020 ◽

Author(s):

Hong Liu ◽

Wenjie Xu ◽

Vincent M. Bruno ◽

Quynh T. Phan ◽

Norma V. Solis ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Secondary Metabolites ◽

Invasive Aspergillosis ◽

Aspergillus Fumigatus ◽

Transcriptional Profiling ◽

Transcriptional Response ◽

Transcription Factor Genes

AbstractTo gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which governs the ability of the organism to proliferate in the lung. The other was ace1, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the Δace1 mutant is due to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.Author summaryAlthough A. fumigatus causes the majority of cases of invasive aspergillosis, the function of most of the genes in its genome remains unknown. To identify genes encoding transcription factors that may be important for virulence, we used a NanoString nCounter to measure the mRNA levels of A. fumigatus transcription factor genes in the lungs of mice with invasive aspergillosis. The transcriptional profiling data indicate that the organism is exposed to nutrient limitation and stress during growth in the lungs, and that it responds by up-regulating genes that encode mycotoxins and secondary metabolites. In vitro, this response was most closely mimicked by growth in medium that was deficient in nitrogen, iron and/or zinc. Using the transcriptional profiling data, we identified two transcription factors that govern A. fumigatus virulence. These were RlmA, which is governs proliferation in the lung and Ace1, which controls the production of mycotoxins and secondary metabolites.

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Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure

10.21203/rs.2.16967/v1 ◽

2019 ◽

Author(s):

Haiwei Wang ◽

Xinrui Wang ◽

Liangpu Xu ◽

Hua Cao

Keyword(s):

Heart Failure ◽

Transcription Factor ◽

Transcription Factors ◽

Signaling Pathway ◽

Insulin Signaling ◽

Regulatory Networks ◽

Target Genes ◽

Transcriptional Profiling ◽

Normal Heart ◽

Developmental Progress

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure developmental progress also are largely unclear.Methods: The transcriptional profiling of heart failure was identified from integrated gene expression datasets. The enriched pathways and transcription factors were analyzed using DAVID and GSEA assay. The transcriptional networks were created by Cytoscape.Results: Compared with the normal heart tissues, we found 90 genes were particularly differentially expressed in heart failing tissues, and those genes were associated with multiple metabolism pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in heart failing tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of heart failing tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in heart failing tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were decreased in heart failing tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed the transcription factor MYC and C/EBPβ mediated regulatory networks in heart failing tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the failure developmental progress by literature research. Conclusions: Our results suggested that transcription factor MYC and C/EBPβ played critical roles in heart failure developmental progress. And new heart failure treatments may be developed by targeting MYC and C/EBPβ.

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Transcriptional Profiling Reveals a Critical Role for Gfi1 in STAT3-Dependent Dendritic Cell Development and -Function.

Blood ◽

10.1182/blood.v104.11.3555.3555 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3555-3555

Author(s):

Chozhavendan Rathinam ◽

Robert Geffers ◽

Raif Yuecel ◽

Jan Buer ◽

Karl Welte ◽

...

Keyword(s):

Transcription Factor ◽

Progenitor Cells ◽

Mhc Class Ii ◽

Transcriptional Profiling ◽

Critical Role ◽

Hematopoietic Progenitor Cells ◽

Developmental Defect ◽

Hematopoietic Progenitor ◽

Gm Csf

Abstract Dendritic cells (DCs) comprise heterogenous and functionally diverse populations of antigen presenting cells. Their developmental pathways remain largely unknown. Using a transcriptional profiling approach, we identified Gfi1 as a novel critical transcription factor in GM-CSF-dependent DC differentiation. Gfi1 is expressed in precursor and mature DCs, as seen in Gfi+/GFP mice, in which one Gfi1 allele is replaced by the GFP cDNA. Gfi1−/ − mice showed a global reduction of myeloid and lymphoid DCs in all lymphoid organs whereas epidermal Langerhans cells were enhanced in number. Gfi1−/ − DCs showed marked phenotypic and functional alterations, as exemplified by decreased MHC class II expression, absent upregulation of costimulatory molecules upon stimulation and reduced ability to stimulate specific T-cell responses. In contrast, Gfi1−/ − DCs exhibited an increased activation profile as assessed by enhanced secretion of IL12. In vitro, Gfi1−/ − hematopoietic progenitor cells were unable to develop into DCs in the presence of GM-CSF or Flt3L. Instead, they differentiated into macrophages, as evidenced by morphology, expression of cell surface markers, and functional properties. These findings suggest that Gfi1 is a critical modulator of DC versus macrophage development. Analysis of hematopoietic chimeras upon transplantation into congenic recipient mice established a cell-autonomous and non-redundant role for Gfi1 in DC development. Furthermore, upon retroviral gene transfer into Gfi1−/ − progenitor cells, the developmental defect could be reconstituted in vitro and in vivo. The inability of Gfi1−/ − hematopoietic progenitor cells to develop into DCs was associated with decreased STAT3 activation, as shown by Western blot and EMSA assays. In conclusion, we have identified Gfi1 as a critical transcription factor that controls DC versus macrophage development and dissociates DC maturation and -activation.

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Identification of MglA-Regulated Genes Reveals Novel Virulence Factors in Francisella tularensis

Infection and Immunity ◽

10.1128/iai.01250-06 ◽

2006 ◽

Vol 74 (12) ◽

pp. 6642-6655 ◽

Cited By ~ 112

Author(s):

Anna Brotcke ◽

David S. Weiss ◽

Charles C. Kim ◽

Patrick Chain ◽

Stephanie Malfatti ◽

...

Keyword(s):

Transcription Factor ◽

Virulence Factors ◽

Francisella Tularensis ◽

Type Strain ◽

Virulence Genes ◽

Wild Type Strain ◽

Transcriptional Profiling ◽

Intracellular Bacterium ◽

Wild Type

ABSTRACT The facultative intracellular bacterium Francisella tularensis causes the zoonotic disease tularemia. F. tularensis resides within host macrophages in vivo, and this ability is essential for pathogenesis. The transcription factor MglA is required for the expression of several Francisella genes that are necessary for replication in macrophages and for virulence in mice. We hypothesized that the identification of MglA-regulated genes in the Francisella genome by transcriptional profiling of wild-type and mglA mutant bacteria would lead to the discovery of new virulence factors utilized by F. tularensis. A total of 102 MglA-regulated genes were identified, the majority of which were positively regulated, including all of the Francisella pathogenicity island (FPI) genes. We mutated novel MglA-regulated genes and tested the mutants for their ability to replicate and induce cytotoxicity in macrophages and to grow in mice. Mutations in MglA-regulated genes within the FPI (pdpB and cds2) as well as outside the FPI (FTT0989, oppB, and FTT1209c) were either attenuated or hypervirulent in macrophages compared to the wild-type strain. All of these mutants exhibited decreased fitness in vivo in competition experiments with wild-type bacteria. We have identified five new Francisella virulence genes, and our results suggest that characterizations of additional MglA-regulated genes will yield further insights into the pathogenesis of this bacterium.

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