scholarly journals Expression and Regulation of Transcription Factors GATA-4 and GATA-6 in Developing Mouse Testis1

Endocrinology ◽  
1999 ◽  
Vol 140 (3) ◽  
pp. 1470-1480 ◽  
Author(s):  
Ilkka Ketola ◽  
Nafis Rahman ◽  
Jorma Toppari ◽  
Malgorzata Bielinska ◽  
Susan B. Porter-Tinge ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulation Of Transcription

scholarly journals Novel Transcriptional Mechanisms for Regulating Metabolism by Thyroid Hormone

2018 ◽  
Vol 19 (10) ◽  
pp. 3284 ◽  
Author(s):  
Brijesh Kumar Singh ◽  
Rohit Anthony Sinha ◽  
Paul Michael Yen
Keyword(s):  
Transcription Factors ◽  
Thyroid Hormone ◽  
Target Genes ◽  
Regulation Of Transcription ◽  
Post Translational Modification ◽  
Hormone Response Elements ◽  
Conventional View ◽  
Metabolic Genes ◽  
Activation Of Transcription ◽  
Rna Transcript

The thyroid hormone plays a key role in energy and nutrient metabolisms in many tissues and regulates the transcription of key genes in metabolic pathways. It has long been believed that thyroid hormones (THs) exerted their effects primarily by binding to nuclear TH receptors (THRs) that are associated with conserved thyroid hormone response elements (TREs) located on the promoters of target genes. However, recent transcriptome and ChIP-Seq studies have challenged this conventional view as discordance was observed between TH-responsive genes and THR binding to DNA. While THR association with other transcription factors bound to DNA, TH activation of THRs to mediate effects that do not involve DNA-binding, or TH binding to proteins other than THRs have been invoked as potential mechanisms to explain this discrepancy, it appears that additional novel mechanisms may enable TH to regulate the mRNA expression. These include activation of transcription factors by SIRT1 via metabolic actions by TH, the post-translational modification of THR, the THR co-regulation of transcription with other nuclear receptors and transcription factors, and the microRNA (miR) control of RNA transcript expression to encode proteins involved in the cellular metabolism. Together, these novel mechanisms enlarge and diversify the panoply of metabolic genes that can be regulated by TH.

scholarly journals Transcriptional Regulation of Hydrogen Peroxide and Calcium for Signaling Transduction and Stress-defensive Genes Contributing to Improved Drought Tolerance in Creeping Bentgrass

2020 ◽  
Vol 145 (4) ◽  
pp. 236-246
Author(s):  
Zhou Li ◽  
Yan Peng ◽  
Bingru Huang
Keyword(s):  
Transcription Factors ◽  
Drought Stress ◽  
Drought Tolerance ◽  
Creeping Bentgrass ◽  
Grass Species ◽  
Regulation Of Transcription ◽  
Signaling Transduction ◽  
Genes Expression ◽  
Protective Genes ◽  
Ca Signaling

Small molecules, including H2O2 and Ca, mediate stress signaling and drought tolerance in plants. The objective of this study was to determine whether improvement in drought tolerance by H2O2 and Ca were associated with the regulation of transcription factors and stress-protective genes in perennial grass species. Plants of creeping bentgrass (Agrostis stolonifera) were sprayed with water (control), H2O2 (9 mm), or CaCl2 (10 mm) and exposed to drought stress for 20 days in controlled-environment growth chambers. Foliar application of H2O2 or Ca led to significant improvement in drought tolerance of creeping bentgrass, as demonstrated by greater turf quality, leaf relative water content, chlorophyll content, photochemical efficiency, and cell membrane stability, as compared with the untreated control. The application of H2O2 and Ca resulted in significant up-regulation of genes in Ca signaling transduction pathways [Ca-dependent kinase 26 (CDPK26), mitogen-activated protein kinase 1 (MAPK1), and 14-3-3] and transcript factors (WRKY75 and MYB13). For genes encoding antioxidant enzymes, H2O2 mainly enhanced superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and dehydroascorbate reductase (DHAR) expression, while Ca primarily improved transcript levels of SOD, monodehydroascorbate reductase (MDHAR), and GR. In addition, heat shock protein 70 (HSP70), metallothionein 1 (MT1), and glutamine synthetase 2 (GS2) were also markedly up-regulated by H2O2 and Ca under drought stress. However, the transcript level of lipoxygenase 3 (LOX3) was significantly down-regulated by H2O2 and Ca under well-watered and drought conditions. These results imply that H2O2 and Ca commonly or differentially regulate genes expression in association with drought tolerance through activating Ca signaling pathway and regulating transcription factors and stress-protective genes expression, leading to the alleviation of lipid peroxidation, maintenance of correct protein folding and translocation, and enhancement of nitrogen metabolism under a prolonged period of drought stress in creeping bentgrass.

scholarly journals Posttranscriptional regulation of T helper cell fate decisions

2018 ◽  
Vol 217 (8) ◽  
pp. 2615-2631 ◽  
Author(s):  
Kai P. Hoefig ◽  
Vigo Heissmeyer
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
T Cell ◽  
Cell Fate ◽  
T Helper Cell ◽  
T Cell Subsets ◽  
Helper Cell ◽  
Regulation Of Transcription ◽  
T Helper ◽  
Cell Fate Decisions

T helper cell subsets orchestrate context- and pathogen-specific responses of the immune system. They mostly do so by secreting specific cytokines that attract or induce activation and differentiation of other immune or nonimmune cells. The differentiation of T helper 1 (Th1), Th2, T follicular helper, Th17, and induced regulatory T cell subsets from naive T cells depends on the activation of intracellular signal transduction cascades. These cascades originate from T cell receptor and costimulatory receptor engagement and also receive critical input from cytokine receptors that sample the cytokine milieu within secondary lymphoid organs. Signal transduction then leads to the expression of subset-specifying transcription factors that, in concert with other transcription factors, up-regulate downstream signature genes. Although regulation of transcription is important, recent research has shown that posttranscriptional and posttranslational regulation can critically shape or even determine the outcome of Th cell differentiation. In this review, we describe how specific microRNAs, long noncoding RNAs, RNA-binding proteins, and ubiquitin-modifying enzymes regulate their targets to skew cell fate decisions.

scholarly journals Regulation of Transcription Factors and Repression of Sp1 by Prolactin Signaling Through the Short Isoform of Its Cognate Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3327-3335 ◽  
Author(s):  
Y. Sangeeta Devi ◽  
Aurora Shehu ◽  
Carlos Stocco ◽  
Julia Halperin ◽  
Jamie Le ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathway ◽  
Short Form ◽  
Binding Activity ◽  
In Vivo Model ◽  
Regulation Of Transcription ◽  
Signaling Mechanism ◽  
Dna Binding Activity ◽  
And Function

Prolactin (PRL) affects the development and function of the reproductive system by binding to two types of receptors, which differ by the size of their intracellular domain in rodents. Whereas the signaling pathway through the long form of the receptor (PRL-RL) is well characterized, signaling through the short form (PRL-RS) remains obscure. In this investigation, we examined transcription factors regulated by PRL in the ovary and decidua of mice expressing only PRL-RS in a PRL receptor null background. These mice provide a powerful in vivo model to study the selective signaling mechanism of PRL through PRL-RS independent of PRL-RL. We also examined the regulation of transcription factors in ovarian and uterine cell lines stably transfected with PRL-RS or PRL-RL. We focused our investigation on transcription factors similarly regulated in both these tissues and clearly established that signaling through PRL-RS does not activate the JaK/Stat in vivo but leads to severe down-regulation of Sp1 expression, DNA binding activity, and nuclear localization, events that appear to involve the calmodulin-dependent protein kinase pathway. Our in vivo and in culture data demonstrate that the PRL-RS activates a signaling pathway distinct from that of the PRL-RL.

scholarly journals Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

2007 ◽  
Vol 293 (2) ◽  
pp. L480-L490 ◽  
Author(s):  
Jinming Zhao ◽  
Richart Harper ◽  
Aaron Barchowsky ◽  
Y. P. Peter Di
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Binding ◽  
Signaling Pathways ◽  
Tobacco Smoke ◽  
Mapk Signaling ◽  
Regulation Of Transcription ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Mapk Signaling Pathways

Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.

The Hexosamine Biosyntheic Pathway and Platinum-Ethylenedicysteine-Glucosamine (Pt-ECG) for Targeted Therapy in Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 587-587
Author(s):  
Lan V Pham ◽  
Jerry Bryant ◽  
Archito T. Tamayo ◽  
Richard Mendez ◽  
Edna Chum ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
Cancer Biology ◽  
Biosynthetic Pathway ◽  
B Cell Lymphoma ◽  
Regulation Of Transcription ◽  
Growth And Survival ◽  
Lead Compounds ◽  
Hexosamine Pathway ◽  
Large B Cell

Abstract Abstract 587 Aggressive non-Hodgkin lymphomas (NHL), such as diffuse large B cell lymphomas (DLBCL), are very common in the US with increasing incidences. Although these lymphomas are now potentially curable, almost half the treated patients still develop relapsed/refractory disease with poor survival outcomes, indicating an urgent need for better therapeutic approaches with improved efficacy. The hexosamine signaling pathway terminating in O-linked N-acetyl glucosamine (O-GlcNAc) cycling has been implicated in cellular signaling cascades and regulation of transcription factors involved in cancer biology. Biological functions of the hexosamine biosynthetic signaling pathways need elucidation, to determine whether altered O-GlcNAc metabolism plays a significant role in hematologic tumors such as DLBCL, and utilize this bifunctional pathway as a targeted therapeutic strategy in DLBCL. We have identified key enzymes of the hexosamine biosynthetic pathways to be highly-expressed in DLBCL cell lines and patient tumor cells. In contrast to normal circulating and tonsillar B cells, DLBCL cells expressed high levels of the rate limiting enzyme glutamine: fructose-6-phosphate amidotransferase (GFAT) as well as terminating enzyme O-GlcNAc transferase (OGT). We discovered that several key growth and survival transcription factors, such as NF-kB and NFAT, known to be highly-activated in DLBCL, are linked to the hexoasmine biosynthetic pathway. We demonstrated that both NF-kB (p65) and NFATc1 directly associated with OGT, and down-regulation of OGT by siRNA inhibits these transcription factors activation, suggesting that both NF-kB-p65 and NFATc1 require O-GlcNAc glycosylation by OGT for their activation. ChiP on Chip analysis on NFATc1 indicated that this transcription factor regulates a set of genes involved in glucose metabolism, including hexokinase and GFAT. These results suggest that the hexosamine pathway is highly active and utilized in DLBCL, and that exploiting this bi-functional pathway(s) as a therapeutic approach is feasible. We have previously developed an imaging agent, 99mTc-ethylenedicysteine-glucosamine (99mTc-EC-G) because EC-G mimics phosphorylated N-acetylglucosamine. ECG treatment in DLBCL cells enhances p65 and NFATc1 nuclear translocation. For therapeutic strategies, we developed metallic unlabeled Platinum (Pt) derivatives-EC-G as potential therapeutic agents. Pre-clinical in vitro studies have shown that our two lead compounds, Pt- and Pt-(DACH)-EC-G effectively inhibit lymphoma cell growth and induce apoptosis. These lead compounds can also induce DNA damage in DLBCL cells, through the up-regulation of phosphorylated histone 2AX (pH2AX), leading to the disruption of p65 and NFATc1 binding to DNA. This data importantly demonstrates that the hexosamine biosynthetic pathway is linked to key growth and survival pathways involved in the pathophysiology of DLBCL. Targeting these pathways with novel platinum EC-G compounds as a theranostic approach should lead to new, more effective treatments and diagnosis for DLBCL, particularly for relapsed/refractory DLBCL. Disclosures: Rollo: Cell Point: Employment.

New Approaches for Mapping Epigenome Dynamics

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-21-SCI-21
Author(s):  
Steven Henikoff
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Conflicts Of Interest ◽  
Regulation Of Transcription ◽  
Base Pairs ◽  
Simple Method ◽  
Genome Wide ◽  
Resolution Mapping

Abstract The protein complexes that package our genomes must be mobilized for active processes to occur, including replication and transcription, but until recently we have only had a static, low resolution view of the "epigenome". Genomes are packaged into nucleosomes, octamers of four core histones wrapped by 147 base pairs of DNA. Nucleosomes present obstacles to transcription, which over genes is the RNA Polymerase II (RNAPII) complex, and one current challenge is to understand what happens to a nucleosome when RNAPII transcribes through the DNA that it occupies. We study this process by developing methods for following nucleosomes as they are evicted and replaced. Among the factors that we have implicated in the process is torsional stress, which we can now measure genome-wide. RNAPII movement can unwrap nucleosomes and thus destabilize them, causing them to be occasionally evicted and replaced. Interestingly, we find that destabilization of nucleosomes during transcription is enhanced by anthracycline compounds, widely used chemotherapeutic drugs that intercalate between DNA base pairs, thus suggesting a new mechanism for cell killing during chemotherapy. We are also interested in what happens to RNAPII during its encounter with a nucleosomes. In vitro, RNAPII cannot transcribe completely through a nucleosome, but rather stalls as it tries to unwrap the DNA from around the core. We have been studying this process in vivo, and have developed a simple method for precisely mapping RNAPII genome-wide. We have used this method to show exactly where RNAPII stalls as it unwraps a nucleosome in vivo, surprisingly in a different place in vivo from where it stalls in vitro. We also have discovered that a variant histone, H2A.Z, which is found in essentially all eukaryotes, helps to reduce the nucleosome barrier to transcription, and in this way may modulate transcription. Other protein components of the epigenome involved in dynamic processes are nucleosome remodelers, which use the energy of ATP to slide or even evict nucleosomes from DNA. Some remodelers help RNAPII get started and others help it overcome the nucleosome barrier to transcription, and by mapping them at base-pair resolution, we can gain insight into how they act. We have also applied our high-resolution mapping tools to transcription factors, which bind DNA at specific sites to regulate transcription and other processes. Our ability to achieve high spatial and temporal resolution mapping of the binding and action of nucleosomes, transcription factors, remodelers and RNAPII provides us with a detailed picture of epigenome dynamics. By using these tools we are beginning to understand how DNA sequence and conformation are recognized for regulation of transcription and other epigenomic processes. Disclosures No relevant conflicts of interest to declare.

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