The Turkey Transcription Factor Pit-1/GHF-1 Can Activate the Turkey Prolactin and Growth Hormone Gene Promoters in Vitro but Is Not Detectable in Lactotrophs in Vivo

2001 ◽  
Vol 123 (3) ◽  
pp. 244-253 ◽  
Author(s):  
Kristy L. Weatherly ◽  
Ramachandran Ramesh ◽  
Heather Strange ◽  
Kerry L. Waite ◽  
Brian Storrie ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transcription Factor ◽  
Growth Hormone Gene ◽  
Gene Promoters

scholarly journals A Nucleoprotein Complex Containing Sp1, C/EBPβ, and HMGI-Y Controls Human Insulin Receptor Gene Transcription

2003 ◽  
Vol 23 (8) ◽  
pp. 2720-2732 ◽  
Author(s):  
Daniela Foti ◽  
Rodolfo Iuliano ◽  
Eusebio Chiefari ◽  
Antonio Brunetti
Keyword(s):  
Transcription Factor ◽  
Insulin Receptor ◽  
Transcriptional Activation ◽  
Receptor Gene ◽  
Gene Promoters ◽  
Insulin Receptor Gene ◽  
Human Insulin Receptor ◽  
Nucleoprotein Complex

ABSTRACT HMGI-Y is an architectural transcription factor that regulates gene expression in vivo by controlling the formation of stereospecific multiprotein complexes on the AT-rich regions of certain gene promoters. Recently, we demonstrated that HMGI-Y is required for proper transcription of the insulin receptor (IR) gene. Here we provide evidence that transcriptional activation of the human IR promoter requires the assembly of a transcriptionally active multiprotein-DNA complex which includes, in addition to HMGI-Y, the ubiquitously expressed transcription factor Sp1 and the CCAAT-enhancer binding protein β (C/EBPβ). Functional integrity of this nucleoprotein complex is required for full transactivation of the IR gene by Sp1 and C/EBPβ in cells readily expressing IRs. We show that HMGI-Y physically interacts with Sp1 and C/EBPβ and facilitates the binding of both factors to the IR promoter in vitro. Furthermore, HMGI-Y is needed for transcriptional synergism between these factors in vivo. Repression of HMGI-Y function adversely affects both Sp1- and C/EBPβ-induced transactivation of the IR promoter. Together, these findings demonstrate that HMGI-Y plays significant molecular roles in the transcriptional activities of these factors in the context of the IR gene and provide concordant support for the hypothesis that, in affected individuals, a putative defect in these nuclear proteins may cause decreased IR expression with subsequent impairment of insulin signaling and action.

Retinoblastoma Protein and the Leukemia-Associated PLZF Transcription Factor Interact To Repress Target Gene Promoters.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1240-1240
Author(s):  
Kevin R. Petrie ◽  
Fabien Guidez ◽  
Jun Zhu ◽  
Gareth Owen ◽  
Yat Peng Chew ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Transcriptional Repression ◽  
Cell Biology ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Gene Promoters ◽  
Cell Commitment

Abstract Translocations of the retinoic acid receptor alpha (RARA) locus with the PLZF or PML genes lead to expression of oncogenic PLZF-RARα or PML-RARα fusion proteins, respectively. These fusion oncoproteins constitutively repress RARα target genes, in large part through aberrant recruitment of multiprotein co-repressor complexes. PML and PML-RARα have previously been shown to associate with the retinoblastoma (Rb) tumour suppressor protein in its hypophosphorylated state. Here we demonstrate that PLZF also interacts with Rb in vitro and in vivo. The interaction between PLZF and Rb is mediated through the Rb pocket and the region of PLZF that lies between its transcriptional repression (POZ) and DNA binding (zinc-finger) domains. Additionally, Rb can simultaneously interact with PLZF and the E2F1 S phase-inducing transcription factor, suggesting that these proteins can exist in the same multiprotein complex. In contrast to the interaction between PML or E2F1 with Rb, the PLZF-Rb interaction is not dependent on hypophosphorylation of Rb. The interaction between PLZF and Rb is further underlined by chromatin immunoprecipitation analysis of PLZF binding to genomic DNA, which shows that PLZF associates with genes controlling cell proliferation known to be regulated by Rb and E2F (for example cdc6). Co-expression of PLZF and Rb results in enhancement of transcriptional repression of PLZF and E2F target genes, indicating functional co-operation between the two proteins. Both PLZF and Rb have been shown to have roles in stem cell biology and, taken together, these data provide a plausible scenario in which interactions between PLZF and Rb function in stem cell commitment or maintenance and self-renewal. The oncogenic PLZF-RARα fusion also interacts with Rb, suggesting that deregulation of Rb function may be a factor in the molecular pathogenesis of PLZF-RARα associated acute promyelocytic leukemia.

scholarly journals Acetylation of Androgen Receptor Enhances Coactivator Binding and Promotes Prostate Cancer Cell Growth

2003 ◽  
Vol 23 (23) ◽  
pp. 8563-8575 ◽  
Author(s):  
Maofu Fu ◽  
Mahadev Rao ◽  
Chenguang Wang ◽  
Toshiyuki Sakamaki ◽  
Jian Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Androgen Receptor ◽  
Hdac Inhibitors ◽  
Growth Control ◽  
Cellular Growth ◽  
Gene Promoters ◽  
P300 Binding

ABSTRACT Modification by acetylation occurs at ε-amino lysine residues of histones and transcription factors. Unlike phosphorylation, a direct link between transcription factor acetylation and cellular growth or apoptosis has not been established. We show that the nuclear androgen receptor (AR), a DNA-binding transcriptional regulator, is acetylated in vivo. The acetylation of the AR is induced by ligand dihydrotestosterone and by histone deacetylase (HDAC) inhibitors in living cells. Direct AR acetylation augmented p300 binding in vitro. Constructs mimicking neutral polar substitution acetylation (ARK630Q, ARK630T) enhanced p300 binding and reduced N-CoR/HDAC/Smad3 corepressor binding, whereas charged residue substitution (ARK630R) reduced p300 binding and enhanced corepressor binding. The AR acetylation mimics promoted cell survival and growth of prostate cancer cells in soft agar and in nude mice and augmented transcription of a subset of growth control target gene promoters. Thus, transcription factor acetylation regulates coactivator/corepressor complex binding, altering expression of specific growth control genes to promote aberrant cellular growth in vivo.

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 Integrin α3β1 Promotes Invasive and Metastatic Properties of Breast Cancer Cells through Induction of the Brn-2 Transcription Factor

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Rakshitha Pandulal Miskin ◽  
Janine S. A. Warren ◽  
Abibatou Ndoye ◽  
Lei Wu ◽  
John M. Lamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Akt Inhibitor ◽  
Integrin Α3β1

In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction of the transcription factor, Brain-2 (Brn-2). We show that RNAi-mediated suppression of α3β1 in MDA-MB-231 cells caused reduced expression of Brn-2 mRNA and protein and reduced activity of the BRN2 gene promoter. In addition, RNAi-targeting of Brn-2 in MDA-MB-231 cells decreased invasion in vitro and lung colonization in vivo, and exogenous Brn-2 expression partially restored invasion to cells in which α3β1 was suppressed. α3β1 promoted phosphorylation of Akt in MDA-MB-231 cells, and treatment of these cells with a pharmacological Akt inhibitor (MK-2206) reduced both Brn-2 expression and cell invasion, indicating that α3β1-Akt signaling contributes to Brn-2 induction. Analysis of RNAseq data from patients with invasive breast carcinoma revealed that high BRN2 expression correlates with poor survival. Moreover, high BRN2 expression positively correlates with high ITGA3 expression in basal-like breast cancer, which is consistent with our experimental findings that α3β1 induces Brn-2 in TNBC cells. Together, our study demonstrates a pro-invasive/pro-metastatic role for Brn-2 in breast cancer cells and identifies a role for integrin α3β1 in regulating Brn-2 expression, thereby revealing a novel mechanism of integrin-dependent breast cancer cell invasion.

scholarly journals Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1343
Author(s):  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Vishnu Raj ◽  
Abdullah T. Alhassani ◽  
Ahmad S. Alhassani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activity Index ◽  
Nigella Sativa ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ppar Γ ◽  
Anti Inflammatory ◽  
Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

scholarly journals Parallel G-quadruplexes recruit the HSV-1 transcription factor ICP4 to promote viral transcription in herpes virus-infected human cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ilaria Frasson ◽  
Paola Soldà ◽  
Matteo Nadai ◽  
Sara Lago ◽  
Sara N. Richter
Keyword(s):  
Transcription Factor ◽  
Early Gene ◽  
Proximity Ligation Assay ◽  
Gene Promoters ◽  
Herpes Simplex Virus 1 ◽  
Direct Binding ◽  
Simplex Virus ◽  
In Cells ◽  
Hsv 1

AbstractG-quadruplexes (G4s) are four-stranded nucleic acid structures abundant at gene promoters. They can adopt several distinctive conformations. G4s have been shown to form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4, the major HSV-1 transcription factor, as the protein that most efficiently interacts with viral G4s during infection. ICP4 specific and direct binding and unfolding of parallel G4s, including those present in HSV-1 immediate early gene promoters, induced transcription in vitro and in infected cells. This mechanism was also exploited by ICP4 to promote its own transcription. Proximity ligation assay allowed visualization of G4-protein interaction at the single selected G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.

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