Faculty Opinions recommendation of Activated signal transduction kinases frequently occupy target genes.

AbstractTrees in temperate regions exhibit evident seasonal patterns, which play vital roles in their growth and development. The activity of cambial stem cells is the basis for regulating the quantity and quality of wood, which has received considerable attention. However, the underlying mechanisms of these processes have not been fully elucidated. Here we performed a comprehensive analysis of morphological observations, transcriptome profiles, the DNA methylome, and miRNAs of the cambium in Populus tomentosa during the transition from dormancy to activation. Anatomical analysis showed that the active cambial zone exhibited a significant increase in the width and number of cell layers compared with those of the dormant and reactivating cambium. Furthermore, we found that differentially expressed genes associated with vascular development were mainly involved in plant hormone signal transduction, cell division and expansion, and cell wall biosynthesis. In addition, we identified 235 known miRNAs and 125 novel miRNAs. Differentially expressed miRNAs and target genes showed stronger negative correlations than other miRNA/target pairs. Moreover, global methylation and transcription analysis revealed that CG gene body methylation was positively correlated with gene expression, whereas CHG exhibited the opposite trend in the downstream region. Most importantly, we observed that the number of CHH differentially methylated region (DMR) changes was the greatest during cambium periodicity. Intriguingly, the genes with hypomethylated CHH DMRs in the promoter were involved in plant hormone signal transduction, phenylpropanoid biosynthesis, and plant–pathogen interactions during vascular cambium development. These findings improve our systems-level understanding of the epigenomic diversity that exists in the annual growth cycle of trees.

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β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

BioMed Research International ◽

10.1155/2015/726012 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Catherina A. Cuevas ◽

Cheril Tapia-Rojas ◽

Carlos Cespedes ◽

Nibaldo C. Inestrosa ◽

Carlos P. Vio

Keyword(s):

Blood Pressure ◽

Signal Transduction ◽

Single Dose ◽

Signaling Pathway ◽

Renal Fibrosis ◽

Target Genes ◽

Hypertensive Rats ◽

Collagen Types ◽

Dependent Signaling Pathway ◽

Pyrvinium Pamoate

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect. Sinceβ-catenin signal transduction participates in fibrotic processes, we evaluated the contribution ofβ-catenin-dependent signaling pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks). The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg (P<0.05), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg,P>0.05). The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats. The expressions ofβ-catenin, p-Ser9-GSK-3beta, and theβ-catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments (P<0.05). In this study we provided evidence thatβ-catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.

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Genome-Wide Identification of Long Non-coding RNA in Trifoliate Orange (Poncirus trifoliata (L.) Raf) Leaves in Response to Boron Deficiency

International Journal of Molecular Sciences ◽

10.3390/ijms20215419 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5419 ◽

Cited By ~ 4

Author(s):

Gao-Feng Zhou ◽

Li-Ping Zhang ◽

Bi-Xian Li ◽

Ou Sheng ◽

Qing-Jiang Wei ◽

...

Keyword(s):

Signal Transduction ◽

Plant Hormones ◽

Target Genes ◽

Expression Patterns ◽

Poncirus Trifoliata ◽

Differentially Expressed ◽

Boron Deficiency ◽

Trifoliate Orange ◽

Genome Wide ◽

A Genome

Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. As a dominant abiotic stress factor in soil, boron (B) deficiency stress has impacted the growth and development of citrus in the red soil region of southern China. In the present work, we performed a genome-wide identification and characterization of lncRNAs in response to B deficiency stress in the leaves of trifoliate orange (Poncirus trifoliata), an important rootstock of citrus. A total of 2101 unique lncRNAs and 24,534 mRNAs were predicted. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed for a total of 16 random mRNAs and lncRNAs to validate their existence and expression patterns. Expression profiling of the leaves of trifoliate orange under B deficiency stress identified 729 up-regulated and 721 down-regulated lncRNAs, and 8419 up-regulated and 8395 down-regulated mRNAs. Further analysis showed that a total of 84 differentially expressed lncRNAs (DELs) were up-regulated and 31 were down-regulated, where the number of up-regulated DELs was 2.71-fold that of down-regulated. A similar trend was also observed in differentially expressed mRNAs (DEMs, 4.21-fold). Functional annotation of these DEMs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and the results demonstrated an enrichment of the categories of the biosynthesis of secondary metabolites (including phenylpropanoid biosynthesis/lignin biosynthesis), plant hormone signal transduction and the calcium signaling pathway. LncRNA target gene enrichment identified several target genes that were involved in plant hormones, and the expression of lncRNAs and their target genes was significantly influenced. Therefore, our results suggest that lncRNAs can regulate the metabolism and signal transduction of plant hormones, which play an important role in the responses of citrus plants to B deficiency stress. Co-expression network analysis indicated that 468 significantly differentially expressed genes may be potential targets of 90 lncRNAs, and a total of 838 matched lncRNA-mRNA pairs were identified. In summary, our data provides a rich resource of candidate lncRNAs and mRNAs, as well as their related pathways, thereby improving our understanding of the role of lncRNAs in response to B deficiency stress, and in symptom formation caused by B deficiency in the leaves of trifoliate orange.

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Multiple phosphorylated forms of the Saccharomyces cerevisiae Mcm1 protein include an isoform induced in response to high salt concentrations.

Molecular and Cellular Biology ◽

10.1128/mcb.17.2.819 ◽

1997 ◽

Vol 17 (2) ◽

pp. 819-832 ◽

Cited By ~ 43

Author(s):

M H Kuo ◽

E T Nadeau ◽

E J Grayhack

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Osmotic Stress ◽

Target Genes ◽

Serum Response Factor ◽

Phosphorylation Site ◽

High Salt ◽

Salt Medium ◽

Membrane Function

The Saccharomyces cerevisiae Mcm1 protein is an essential multifunctional transcription factor which is highly homologous to human serum response factor. Mcm1 protein acts on a large number of distinctly regulated genes: haploid cell-type-specific genes, G2-cell-cycle-regulated genes, pheromone-induced genes, arginine metabolic genes, and genes important for cell wall and cell membrane function. We show here that Mcm1 protein is phosphorylated in vivo. Several (more than eight) isoforms of Mcm1 protein, resolved by isoelectric focusing, are present in vivo; two major phosphorylation sites lie in the N-terminal 17 amino acids immediately adjacent to the conserved MADS box DNA-binding domain. The implications of multiple species of Mcm1, particularly the notion that a unique Mcm1 isoform could be required for regulation of a specific set of Mcm1's target genes, are discussed. We also show here that Mcm1 plays an important role in the response to stress caused by NaCl. G. Yu, R. J. Deschenes, and J. S. Fassler (J. Biol. Chem. 270:8739-8743, 1995) showed that Mcm1 function is affected by mutations in the SLN1 gene, a signal transduction component implicated in the response to osmotic stress. We find that mcm1 mutations can confer either reduced or enhanced survival on high-salt medium; deletion of the N terminus or mutation in the primary phosphorylation site results in impaired growth on high-salt medium. Furthermore, Mcm1 protein is a target of a signal transduction system responsive to osmotic stress: a new isoform of Mcm1 is induced by NaCl or KCl; this result establishes that Mcm1 itself is regulated.

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Hairless-Mediated Repression of Notch Target Genes Requires the Combined Activity of Groucho and CtBP Corepressors

Molecular and Cellular Biology ◽

10.1128/mcb.25.23.10433-10441.2005 ◽

2005 ◽

Vol 25 (23) ◽

pp. 10433-10441 ◽

Cited By ~ 86

Author(s):

Anja C. Nagel ◽

Alena Krejci ◽

Gennady Tenin ◽

Alejandro Bravo-Patiño ◽

Sarah Bray ◽

...

Keyword(s):

Signal Transduction ◽

Target Genes ◽

Transcriptional Regulators ◽

Dna Binding Protein ◽

The Other ◽

Binding Motif ◽

Binding Motifs ◽

Notch Intracellular Domain ◽

Second Mode ◽

Notch Activation

ABSTRACT Notch signal transduction centers on a conserved DNA-binding protein called Suppressor of Hairless [Su(H)] in Drosophila species. In the absence of Notch activation, target genes are repressed by Su(H) acting in conjunction with a partner, Hairless, which contains binding motifs for two global corepressors, CtBP and Groucho (Gro). Usually these corepressors are thought to act via different mechanisms; complexed with other transcriptional regulators, they function independently and/or redundantly. Here we have investigated the requirement for Gro and CtBP in Hairless-mediated repression. Unexpectedly, we find that mutations inactivating one or the other binding motif can have detrimental effects on Hairless similar to those of mutations that inactivate both motifs. These results argue that recruitment of one or the other corepressor is not sufficient to confer repression in the context of the Hairless-Su(H) complex; Gro and CtBP need to function in combination. In addition, we demonstrate that Hairless has a second mode of repression that antagonizes Notch intracellular domain and is independent of Gro or CtBP binding.

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Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae

Eukaryotic Cell ◽

10.1128/ec.3.1.221-231.2004 ◽

2004 ◽

Vol 3 (1) ◽

pp. 221-231 ◽

Cited By ~ 100

Author(s):

Aneta Kaniak ◽

Zhixiong Xue ◽

Daniel Macool ◽

Jeong-Ho Kim ◽

Mark Johnston

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Transcription Factor ◽

Regulatory Network ◽

Target Genes ◽

Glucose Repression ◽

Signal Transduction Pathways ◽

Glucose Signaling ◽

Genes Encoding ◽

Glucose Induction

ABSTRACT The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.

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SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

10.1101/2021.09.08.459466 ◽

2021 ◽

Author(s):

Julie Gamart ◽

Iros Barozzi ◽

Frédéric Laurent ◽

Robert Reinhardt ◽

Laurène Ramos Martins ◽

...

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Transcriptional Regulation ◽

Target Genes ◽

Cholesterol Biosynthesis ◽

Limb Bud ◽

Positive Role ◽

Shh Signaling ◽

Bud Development ◽

Repressive Effect

ABSTRACTSMAD4 regulates gene expression in response to BMP and TGFβ signal transduction and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we use an epitope-tagged Smad4 allele for ChIP-seq analysis together with transcriptome analysis of wild-type and mouse forelimb buds lacking Smad4 in the mesenchyme. This analysis identifies the SMAD4 target genes during establishment of the feedback signaling system and establishes that SMAD4 predominantly mediates BMP signal-transduction during early limb bud development. Unexpectedly, the initial analysis reveals that the expression of cholesterol biosynthesis enzymes is precociously down-regulated and intracellular cholesterol levels reduced in Smad4-deficient limb bud mesenchymal progenitors. The SMAD4 target GRNs includes genes, whose expression in the anterior limb bud is up-regulated by interactions of SMAD4 complexes with enhancers active in the anterior mesenchyme. This reveals a predominant function of SMAD4 in up-regulating target gene expression in the anterior limb bud mesenchyme. Analysis of differentially expressed genes that are shared between Smad4- and Shh-deficient limb buds corroborates the positive role of SMAD4 in transcriptional regulation of anterior genes and reveals a repressive effect on posterior genes that are positively regulated by SHH signaling. This analysis uncovers the overall opposing effects of SMAD4-mediated BMP and SHH signalling on transcriptional regulation during early limb bud development. In summary, this analysis indicates that during early digit patterning and limb bud outgrowth, the anterior/proximal and proximo/distal expression dynamics of co-regulated genes are controlled by distinct and contrasting trans-regulatory inputs from SHH and SMAD4-mediated BMP signal transduction.

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Smoothened Transduces Hedgehog Signals via Activity-Dependent Sequestration of PKA Catalytic Subunits

10.1101/2020.07.01.183079 ◽

2020 ◽

Cited By ~ 1

Author(s):

Corvin D. Arveseth ◽

John T. Happ ◽

Danielle S. Hedeen ◽

Ju-Fen Zhu ◽

Jacob L. Capener ◽

...

Keyword(s):

Signal Transduction ◽

Transcription Factors ◽

Target Genes ◽

Catalytic Subunits ◽

Unknown Mechanism ◽

Gli Transcription Factors ◽

Intracellular Domains ◽

G Protein Coupled ◽

Activity Dependent ◽

Kinase A

ABSTRACTThe Hedgehog (Hh) pathway is essential for organ development, homeostasis, and regeneration. Dysfunction of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Here we show that, rather than conforming to traditional GPCR signaling paradigms, SMO activates GLI by binding and sequestering protein kinase A (PKA) catalytic subunits at the membrane. This sequestration, triggered by GPCR kinase 2 (GRK2)-mediated phosphorylation of SMO intracellular domains, prevents PKA from phosphorylating soluble substrates, releasing GLI from PKA-mediated inhibition. Our work provides a mechanism directly linking Hh signal transduction at the membrane to GLI transcription in the nucleus. This process is more fundamentally similar between species than prevailing hypotheses suggest. The mechanism described here may apply broadly to other GPCR- and PKA-containing cascades in diverse areas of biology.

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