scholarly journals The SLIM1 transcription factor regulates arsenic sensitivity in Arabidopsis thaliana

2021 ◽  
Author(s):  
Timothy O. Jobe ◽  
Qi Yu ◽  
Felix Hauser ◽  
Qingqing Xie ◽  
Yuan Meng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Cluster ◽  
Arsenic Exposure ◽  
Redox Status ◽  
Sulfur Assimilation ◽  
Transcriptional Responses ◽  
Critical Function ◽  
Thiol Compounds ◽  
Arsenic Tolerance

AbstractThe transcriptional regulators of arsenic-induced gene expression remain largely unknown; however, arsenic exposure rapidly depletes cellular glutathione levels increasing demand for thiol compounds from the sulfur assimilation pathway. Thus, sulfur assimilation is tightly linked with arsenic detoxification. To explore the hypothesis that the key transcriptional regulator of sulfur assimilation, SLIM1, is involved in arsenic-induced gene expression, we evaluated the response of slim1 mutants to arsenic treatments. We found that slim1 mutants were sensitive to arsenic in root growth assays. Furthermore, arsenic treatment caused high levels of oxidative stress in the slim1 mutants, and slim1 mutants were impaired in both thiol and sulfate accumulation. We also found enhanced arsenic accumulation in the roots of slim1 mutants. Furthermore, microarray analyses identified genes from a highly co-regulated gene cluster (the O-acetylserine gene cluster), as being significantly upregulated in the slim1-1 mutant background in response to arsenic exposure. The present study identified the SLIM1 transcription factor as an important component in arsenic-induced gene expression and arsenic tolerance. Our results suggest that the severe arsenic sensitivity of the slim1 mutants is a result of both altered redox status as well as mis-regulation of key genes.HighlightWe identify a critical function of the SLIM1 transcription factor in regulating arsenic transcriptional responses and propose that SLIM1 acts as both a transcriptional activator and repressor.

scholarly journals The SLIM1 transcription factor regulates arsenic sensitivity in Arabidopsis thaliana

2020 ◽  
Author(s):  
Timothy Jobe ◽  
Qi Yu ◽  
Felix Hauser ◽  
Qingqing Xie ◽  
Yuan Meng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Cluster ◽  
Arsenic Exposure ◽  
Redox Status ◽  
Sulfur Assimilation ◽  
Thiol Compounds ◽  
Arsenic Tolerance ◽  
Arsenic Accumulation ◽  
Arsenic Detoxification

The transcriptional regulators of arsenic-induced gene expression remain largely unknown; however, arsenic exposure rapidly depletes cellular glutathione levels increasing demand for thiol compounds from the sulfur assimilation pathway. Thus, sulfur assimilation is tightly linked with arsenic detoxification. To explore the hypothesis that the key transcriptional regulator of sulfur assimilation, SLIM1, is involved in arsenic-induced gene expression, we evaluated the response of slim1 mutants to arsenic treatments. We found that slim1 mutants were sensitive to arsenic in root growth assays. Furthermore, arsenic treatment caused high levels of oxidative stress in the slim1 mutants, and slim1 mutants were impaired in both thiol and sulfate accumulation. We also found enhanced arsenic accumulation in the roots of slim1 mutants. Furthermore, microarray analyses identified genes from a highly co-regulated gene cluster (the O-acetylserine gene cluster), as being significantly upregulated in the slim1-1 mutant background in response to arsenic exposure. The present study identified the SLIM1 transcription factor as an important component in arsenic-induced gene expression and arsenic tolerance. Our results suggest that the severe arsenic sensitivity of the slim1 mutants is a result of both altered redox status as well as mis-regulation of key genes.

scholarly journals Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

2019 ◽  
Vol 116 (20) ◽  
pp. 9893-9902 ◽  
Author(s):  
Christopher M. Uyehara ◽  
Daniel J. McKay
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Nuclear Receptor ◽  
Binding Sites ◽  
Transcriptional Responses ◽  
Enhancer Activity ◽  
Developmental Transitions ◽  
Experimental Systems ◽  
The Impact

The ecdysone pathway was among the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like other hormones, ecdysone controls gene expression through a nuclear receptor, which functions as a ligand-dependent transcription factor. Although it is clear that ecdysone elicits distinct transcriptional responses within its different target tissues, the role of its receptor, EcR, in regulating target gene expression is incompletely understood. In particular, EcR initiates a cascade of transcription factor expression in response to ecdysone, making it unclear which ecdysone-responsive genes are direct EcR targets. Here, we use the larval-to-prepupal transition of developing wings to examine the role of EcR in gene regulation. Genome-wide DNA binding profiles reveal that EcR exhibits widespread binding across the genome, including at many canonical ecdysone response genes. However, the majority of its binding sites reside at genes with wing-specific functions. We also find that EcR binding is temporally dynamic, with thousands of binding sites changing over time. RNA-seq reveals that EcR acts as both a temporal gate to block precocious entry to the next developmental stage as well as a temporal trigger to promote the subsequent program. Finally, transgenic reporter analysis indicates that EcR regulates not only temporal changes in target enhancer activity but also spatial patterns. Together, these studies define EcR as a multipurpose, direct regulator of gene expression, greatly expanding its role in coordinating developmental transitions.

scholarly journals A direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

2019 ◽  
Author(s):  
Christopher M. Uyehara ◽  
Daniel J. McKay
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dna Binding ◽  
Nuclear Receptor ◽  
Binding Sites ◽  
Target Genes ◽  
Transcriptional Responses ◽  
Developmental Transitions ◽  
The Impact

ABSTRACTThe ecdysone pathway was amongst the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like other hormones, ecdysone controls gene expression through a nuclear receptor, which functions as a ligand-dependent transcription factor. Although it is clear that ecdysone elicits distinct transcriptional responses within its different target tissues, the role of its receptor, EcR, in regulating target gene expression is incompletely understood. In particular, EcR initiates a cascade of transcription factor expression in response to ecdysone, making it unclear which ecdysone-responsive genes are direct EcR targets. Here, we use the larval-to-prepupal transition of developing wings to examine the role of EcR in gene regulation. Genome-wide DNA binding profiles reveal that EcR exhibits widespread binding across the genome, including at many canonical ecdysone-response genes. However, the majority of its binding sites reside at genes with wing-specific functions. We also find that EcR binding is temporally dynamic, with thousands of binding sites changing over time. RNA-seq reveals that EcR acts as both a temporal gate to block precocious entry to the next developmental stage as well as a temporal trigger to promote the subsequent program. Finally, transgenic reporter analysis indicates that EcR regulates not only temporal changes in target enhancer activity but also spatial patterns. Together, these studies define EcR as a multipurpose, direct regulator of gene expression, greatly expanding its role in coordinating developmental transitions.SIGNIFICANCENuclear receptors (NRs) are sequence-specific DNA binding proteins that act as intracellular receptors for small molecules such as hormones. Prior work has shown that NRs function as ligand-dependent switches that initiate a cascade of gene expression changes. The extent to which NRs function as direct regulators of downstream genes in these hierarchies remains incompletely understood. Here, we study the role of the NR EcR in metamorphosis of the Drosophila wing. We find that EcR directly regulates many genes at the top of the hierarchy as well as at downstream genes. Further, we find that EcR binds distinct sets of target genes at different developmental times. This work helps inform how hormones elicit tissue- and temporal-specific responses in target tissues.

scholarly journals The Rab5-Rab11 endosomal pathway is required for BDNF-induced CREB transcriptional regulation in neurons

2019 ◽  
Author(s):  
Andrés G. González ◽  
Oscar M. Lazo ◽  
Francisca C. Bronfman
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Plasma Membrane ◽  
Neurotrophic Factor ◽  
Dendritic Growth ◽  
Signaling Cascades ◽  
Transcriptional Responses ◽  
Recycling Endosomes ◽  
Central Neurons ◽  
Endosomal Pathway

AbstractBrain-derived neurotrophic factor (BDNF) is a key regulator of the morphology and connectivity of central neurons. We have previously shown that BDNF/TrkB signaling regulates the activity and mobility of the GTPases Rab5 and Rab11, which in turn determine the post-endocytic sorting of signaling TrkB receptors. Moreover, altered Rab5 or Rab11 activity inhibits BDNF-induced dendritic branching. Whether Rab5 or Rab11 activity is important for local events only, or also for regulating nuclear signaling and gene expression, is unknown. Here, we investigated whether BDNF-induced signaling cascades were altered when early and recycling endosomes were disrupted by the expression of dominant negative mutants of Rab5 and Rab11. The activities of both Rab5 and Rab11 were required for sustained activity of Erk1/2 and nuclear CREB phosphorylation and for increased transcription of BDNF-dependent genes containing CRE-binding sites that include activity-regulated genes such as Arc, Dusp1, c-fos and Egr1 and growth and survival genes such as Atf3 and Nf1. Based on our results, we propose that the early and recycling endosomes provide a platform for the integration of neurotrophic signaling from the plasma membrane to the nucleus in neurons and that this mechanism likely regulates neuronal plasticity and neuronal survival.Significance StatementBDNF is a soluble neurotrophic factor that regulates plastic changes in the brain, including dendritic growth, by binding to its plasma membrane receptor TrkB. BDNF/TrkB activates signaling cascades leading to activation of CREB, a key transcription factor regulating circuit development and learning and memory. Our results uncover the cellular mechanisms that central neurons use to integrate the signaling of plasma membrane receptors with nuclear transcriptional responses. We found that the endosomal pathway is required for the signaling cascade initiated by BDNF and its receptors in the plasma membranes to modulate BDNF-dependent gene expression and neuronal dendritic growth mediated by the CREB transcription factor in the nucleus.

scholarly journals Commensal Bacteria Regulate Gene Expression and Differentiation in Vertebrate Olfactory Systems Through Transcription Factor REST

2019 ◽  
Vol 44 (8) ◽  
pp. 615-630 ◽  
Author(s):  
Elisa Casadei ◽  
Luca Tacchi ◽  
Colin R Lickwar ◽  
Scott T Espenschied ◽  
James M Davison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Olfactory Epithelium ◽  
Neuronal Development ◽  
Sensory Systems ◽  
Commensal Bacteria ◽  
Promoter Regions ◽  
Transcriptional Responses ◽  
Germ Free

Abstract Sensory systems such as the olfactory system detect chemical stimuli and thereby determine the relationships between the animal and its surroundings. Olfaction is one of the most conserved and ancient sensory systems in vertebrates. The vertebrate olfactory epithelium is colonized by complex microbial communities, but microbial contribution to host olfactory gene expression remains unknown. In this study, we show that colonization of germ-free zebrafish and mice with microbiota leads to widespread transcriptional responses in olfactory organs as measured in bulk tissue transcriptomics and RT-qPCR. Germ-free zebrafish olfactory epithelium showed defects in pseudostratification; however, the size of the olfactory pit and the length of the cilia were not different from that of colonized zebrafish. One of the mechanisms by which microbiota control host transcriptional programs is by differential expression and activity of specific transcription factors (TFs). REST (RE1 silencing transcription factor, also called NRSF) is a zinc finger TF that binds to the conserved motif repressor element 1 found in the promoter regions of many neuronal genes with functions in neuronal development and differentiation. Colonized zebrafish and mice showed increased nasal expression of REST, and genes with reduced expression in colonized animals were strongly enriched in REST-binding motifs. Nasal commensal bacteria promoted in vitro differentiation of Odora cells by regulating the kinetics of REST expression. REST knockdown resulted in decreased Odora cell differentiation in vitro. Our results identify a conserved mechanism by which microbiota regulate vertebrate olfactory transcriptional programs and reveal a new role for REST in sensory organs.

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

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