Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB.

1995 ◽  
Vol 69 (7) ◽  
pp. 4323-4330 ◽  
Author(s):  
Q Zhou ◽  
R W Gedrich ◽  
D A Engel
Keyword(s):  
Transcriptional Repression ◽  
Direct Interaction

scholarly journals BRG1 Controls the Activity of the Retinoblastoma Protein via Regulation of p21CIP1/WAF1/SDI

2004 ◽  
Vol 24 (3) ◽  
pp. 1188-1199 ◽  
Author(s):  
Hyeog Kang ◽  
Kairong Cui ◽  
Keji Zhao
Keyword(s):  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Growth Arrest ◽  
Retinoblastoma Protein ◽  
Direct Interaction ◽  
Physical Interaction ◽  
Cdk Inhibitor ◽  
Regulation Of Cell Cycle

ABSTRACT The ubiquitous mammalian chromatin-remodeling SWI/SNF-like BAF complexes play critical roles in tumorigenesis. It was suggested that the direct interaction of BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle progression by pRB. We present evidence that the BRG1-containing complexes regulate the expression of the cdk inhibitor p21CIP1/WAF1/SDI. Furthermore, we show that the physical interaction between BRG1 and pRB is not required for induction of cell growth arrest and transcriptional repression of E2F target genes by pRB. Instead, BRG1 activates pRB by inducing its hypophosphorylation through up-regulation of the cdk inhibitor p21. The hypophosphorylation of pRB is reinforced by down-regulation of critical components, including cdk2, cyclin E, and cyclin D, in the pRB regulatory network. We demonstrate that up-regulation of p21 by BRG1 is necessary to induce formation of flat cells, growth arrest, and finally, cell senescence. Our results suggest that the BRG1-containing complexes control cellular proliferation and senescence by modulating the pRB pathway via multiple mechanisms.

scholarly journals Transcriptional repression of the gluconeogenic gene PEPCK by the orphan nuclear receptor SHP through inhibitory interaction with C/EBPα

2007 ◽  
Vol 402 (3) ◽  
pp. 567-574 ◽  
Author(s):  
Min Jung Park ◽  
Hee Jeong Kong ◽  
Hye Young Kim ◽  
Hyeong Hoe Kim ◽  
Joon Hong Kim ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Transcriptional Repression ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Regulatory Element ◽  
Direct Interaction ◽  
Orphan Nuclear Receptor ◽  
Hepatic Gluconeogenesis ◽  
Inhibitory Interaction

SHP (short heterodimer partner) is an orphan nuclear receptor that plays an important role in regulating glucose and lipid metabolism. A variety of transcription factors are known to regulate transcription of the PEPCK (phosphoenolpyruvate carboxykinase) gene, which encodes a rate-determining enzyme in hepatic gluconeogenesis. Previous reports identified glucocorticoid receptor and Foxo1 as novel downstream targets regulating SHP inhibition [Borgius, Steffensen, Gustafsson and Treuter (2002) J. Biol. Chem. 277, 49761–49796; Yamagata, Daitoku, Shimamoto, Matsuzaki, Hirota, Ishida and Fukamizu (2004) J. Biol. Chem. 279, 23158–23165]. In the present paper, we show a new molecular mechanism of SHP-mediated inhibition of PEPCK transcription. We also show that the CRE1 (cAMP regulatory element 1; −99 to −76 bp relative to the transcription start site) of the PEPCK promoter is also required for the inhibitory regulation by SHP. SHP repressed C/EBPα (CCAAT/enhancer-binding protein α)-driven transcription of PEPCK through direct interaction with C/EBPα protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPα and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription. Taken together, these results suggest that SHP might regulate a level of hepatic gluconeogenesis driven by C/EBPα activation.

scholarly journals Histone Variant macroH2A1 Spatially and Functionally Organizes Human Papillomavirus Replication Foci in the Productive Stage of Infection

2021 ◽  
Author(s):  
Simran Khurana ◽  
Tovah E. Markowitz ◽  
Juraj Kabat ◽  
Alison A McBride
Keyword(s):  
Viral Replication ◽  
Rna Polymerase Ii ◽  
Transcriptional Repression ◽  
Direct Interaction ◽  
Strand Break ◽  
Histone Variant ◽  
Keratinocyte Differentiation ◽  
Differentiated Cells ◽  
Replication Foci ◽  
Transcription Complexes

The life cycle of HPV depends on keratinocyte differentiation as the virus modulates and takes advantage of cellular pathways to replicate its genome and assemble viral particles in differentiated cells. Viral genomes are amplified in nuclear replication foci in differentiated keratinocytes, and DNA repair factors from the DNA damage response signaling pathway are recruited to replicate viral DNA. The HPV genome is associated with cellular histones at all stages of the infectious cycle, and here we show the histone variant macroH2A1 is bound to the HPV genome and enriched in viral replication foci in differentiated cells. MacroH2A1 isoforms play important roles in cellular transcriptional repression, double strand break repair, and replication stress. The viral E8^E2 protein also binds to the HPV genome and inhibits viral replication and gene expression by recruiting NCoR/SMRT complexes. We show here that E8^E2 and SMRT also localize within replication foci, though not through direct interaction with macroH2A1. Conversely, transcription complexes containing RNA polymerase II and Brd4 are located on the surface of the foci. Foci generated with an HPV16 E8^E2 mutant genome are not enriched for SMRT or macroH2A1 but contain transcriptional complexes throughout the foci. We demonstrate that macroH2A1 promotes viral late transcription and propose that it does so by spatially separating replication and transcription activities within replication foci.

scholarly journals The transcriptional repressor even-skipped interacts directly with TATA-binding protein.

1995 ◽  
Vol 15 (9) ◽  
pp. 5007-5016 ◽  
Author(s):  
M Um ◽  
C Li ◽  
J L Manley
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Binding Protein ◽  
Transcriptional Repressor ◽  
Direct Interaction ◽  
Tata Binding Protein ◽  
Homeodomain Protein ◽  
Repression Domain

The Drosophila homeodomain protein Even-skipped (Eve) has previously been shown to function as a sequence-specific transcriptional repressor, and in vitro and in vivo experiments have shown that the protein can actively block basal transcription. However, the mechanism of repression is not known. Here, we present evidence establishing a direct interaction between Eve and the TATA-binding protein (TBP). Using cotransfection assays with minimal basal promoters whose activity can be enhanced by coexpression of TBP, we found that Eve could efficiently block, or squelch, this enhancement. Squelching did not require Eve DNA-binding sites on the reporter plasmids but was dependent on the presence of the Eve repression domain. Further support for an in vivo interaction between the Eve repression domain and TBP was derived from a two-hybrid-type assay with transfected cells. Evidence that Eve and TBP interact directly was provided by in vitro binding assays, which revealed a specific protein-protein interaction that required an intact Eve repression domain and the conserved C terminus of TBP. The Eve homeodomain was also required for these associations, suggesting that it may function in protein-protein interactions. We also show that a previously characterized artificial repression region behaves in a manner similar to that of the Eve repression domain, including its ability to squelch TBP-enhanced expression in vivo and to bind TBP specifically in vitro. Our results suggest a model for transcriptional repression that involves an interaction between Eve and TBP.

scholarly journals The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns

2011 ◽  
Vol 208 (5) ◽  
pp. 1001-1013 ◽  
Author(s):  
Kenneth J. Oestreich ◽  
Albert C. Huang ◽  
Amy S. Weinmann
Keyword(s):  
Transcriptional Repression ◽  
Expression Patterns ◽  
Direct Interaction ◽  
Gene Repression ◽  
Th1 Cells ◽  
T Helper ◽  
T Box ◽  
Th Cell ◽  
Ifn Γ ◽  
Late Stages

The T-box transcription factor T-bet is important for the differentiation of naive CD4+ T helper cells (Th cells) into the Th1 phenotype. Much is known about T-bet’s role as a transcriptional activator, but less is known about the mechanisms by which T-bet functionally represses alternative Th cell genetic programs. In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet. Significantly, T-bet’s role in the repression of these genes is through a direct interaction with their promoters. Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells. Importantly, T-bet’s novel role in transcriptional repression is because of its ability to physically associate with, and functionally recruit, the transcriptional repressor Bcl-6 to a subset of promoters. Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity. Collectively, these data establish a novel mechanism for T-bet–mediated gene repression in which two lineage-defining transcription factors, one a classical activator and one a repressor, collaborate to promote and properly regulate Th1 development.

scholarly journals TGF-β Signaling Cooperates with AT Motif-Binding Factor-1 for Repression of the α-Fetoprotein Promoter

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Nobuo Sakata ◽  
Satoshi Kaneko ◽  
Souichi Ikeno ◽  
Yutaka Miura ◽  
Hidekazu Nakabayashi ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Inhibitory Action ◽  
Fetal Liver ◽  
Direct Interaction ◽  
Detectable Level ◽  
Dependent Manner ◽  
Reporter System ◽  
Adult Liver ◽  
Binding Factor ◽  
Dose Dependent

α-Fetoprotein (AFP) is known to be highly produced in fetal liver despite its barely detectable level in normal adult liver. On the other hand, hepatocellular carcinoma often shows high expression of AFP. Thus, AFP seems to be an oncogenic marker. In our present study, we investigated how TGF-β signaling cooperates with AT motif-binding factor-1 (ATBF1) to inhibit AFP transcription. Indeed, the expression of AFP mRNA in HuH-7 cells was negatively regulated by TGF-β signaling. To further understand how TGF-β suppresses the transcription of the AFP gene, we analyzed the activity of the AFP promoter in the presence of TGF-β. We found that the TGF-β signaling and ATBF1 suppressed AFP transcription through two ATBF1 binding elements (AT-motifs). Using a heterologous reporter system, both AT-motifs were required for transcriptional repression upon TGF-β stimulation. Furthermore, Smads were found to interact with ATBF1 at both its N-terminal and C-terminal regions. Since the N-terminal (ATBF1N) and C-terminal regions of ATBF1 (ATBF1C) lack the ability of DNA binding, both truncated mutants rescued the cooperative inhibitory action by the TGF-β signaling and ATBF1 in a dose-dependent manner. Taken together, these findings indicate that TGF-β signaling can act in concert with ATBF1 to suppress the activity of the AFP promoter through direct interaction of ATBF1 with Smads.

scholarly journals Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression.

1995 ◽  
Vol 15 (1) ◽  
pp. 227-234 ◽  
Author(s):  
N Horikoshi ◽  
A Usheva ◽  
J Chen ◽  
A J Levine ◽  
R Weinmann ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Binding Protein ◽  
Direct Interaction ◽  
Tata Binding Protein ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Carboxy Terminal

The tumor suppressor gene product p53 can activate and repress transcription. Both transcriptional activation and repression are thought to involve the direct interaction of p53 with the basal transcriptional machinery. Previous work has demonstrated an in vitro interaction between p53 and the TATA-binding protein that requires amino acids 20 to 57 of p53 and amino acids 220 to 271 of the TATA-binding protein. The present results show that a 75-amino-acid segment from the carboxy terminus of p53 also can bind to the TATA-binding protein in vitro, and this interaction requires amino acids 217 to 268 of the TATA-binding protein, essentially the same domain that is required for interaction with the amino-terminal domain of p53. A carboxy-terminal segment of p53 can mediate repression when bound to DNA as a GAL4-p53 fusion protein. The amino- and carboxy-terminal p53 interactions occur within the domain on the TATA-binding protein to which the adenovirus 13S E1A oncoprotein has previously been shown to bind. The 13S E1A oncoprotein can dissociate the complex formed between the carboxy-terminal domain of p53 and the TATA-binding protein and relieve p53-mediated transcriptional repression. These results demonstrate that two independent domains of p53 can potentially interact with the TATA-binding protein, and they define a mechanism--relief of repression--by which the 13S E1A oncoprotein can activate transcription through the TATA motif.

scholarly journals Vibrio cholerae ParE2 toxin modulates its operon transcription by stabilization of an antitoxin DNA ruler

2021 ◽  
Author(s):  
Gabriela Garcia-Rodriguez ◽  
Yana Andrea Girardin ◽  
Ranjan Kumar Singh ◽  
Alexander N. Volkov ◽  
Albert Konijnenberg ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Transcriptional Repression ◽  
Direct Interaction ◽  
Dna Interaction ◽  
Native Mass Spectrometry ◽  
Small Chromosome ◽  
Chromosome Ii ◽  
Toxin Inhibition ◽  
Plasmid Rk2

The parDE2 operon of Vibrio cholerae encodes a type II TA system, which is one of three loci in the superintegron of small chromosome II that show modest similarity to the parDE operon of plasmid RK2. ParE2, like plasmid RK2-encoded ParE, inhibits DNA gyrase, an essential topoisomerase that is also the target of quinolone antibacterial agents. Mechanistic understanding on ParE2 toxin inhibition by direct interaction with its cognate antitoxin and transcriptional autoregulation of the TA system are currently lacking. ParD2, the ribbon-helix-helix (RHH) antitoxin, auto-represses the parDE2 promoter. This repression is enhanced by ParE2, which therefore functions as a transcriptional co-repressor. Here we present protein-DNA interaction studies and high-resolution X-ray structures of the ParD2:ParE2 complex and isolated ParD2 antitoxin, revealing the basis of toxin inhibition and autoregulation of the TA operon by conditional cooperativity. Native mass spectrometry, SAXS and MALS studies confirm the presence of different oligomerization states of ParD2 in solution and the role of the DNA-binding hexameric ParD26:ParE22 assembly in transcriptional repression.

scholarly journals A Conserved α-Helical Motif Mediates the Interaction of Sp1-Like Transcriptional Repressors with the Corepressor mSin3A

2001 ◽  
Vol 21 (15) ◽  
pp. 5041-5049 ◽  
Author(s):  
Jin-San Zhang ◽  
Martin C. Moncrieffe ◽  
Joanna Kaczynski ◽  
Volker Ellenrieder ◽  
Franklyn G. Prendergast ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Transforming Growth Factor ◽  
Direct Interaction ◽  
Helical Structure ◽  
Functional Characteristic ◽  
Transforming Growth Factor Β ◽  
Transcriptional Repressors ◽  
Helix Loop Helix ◽  
Zinc Finger Motifs

ABSTRACT Sp1-like proteins are defined by three highly homologous C2H2 zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor β-inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the α-HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.

scholarly journals CTIP2 Associates with the NuRD Complex on the Promoter of p57KIP2, a Newly Identified CTIP2 Target Gene

2006 ◽  
Vol 281 (43) ◽  
pp. 32272-32283 ◽  
Author(s):  
Acharawan Topark-Ngarm ◽  
Olga Golonzhka ◽  
Valerie J. Peterson ◽  
Brian Barrett ◽  
Brigetta Martinez ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Kinase Inhibitor ◽  
Neuroblastoma Cells ◽  
Direct Interaction ◽  
Binding Activity ◽  
Dependent Manner ◽  
Nurd Complex ◽  
Dna Binding Activity

Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2 (CTIP2), also known as Bcl11b, is a transcriptional repressor that functions by direct, sequence-specific DNA binding activity or by recruitment to the promoter template by interaction with COUP-TF family members. CTIP2 is essential for both T cell development and axonal projections of corticospinal motor neurons in the central nervous system. However, little is known regarding the molecular mechanism(s) by which CTIP2 contributes to either process. CTIP2 complexes that were isolated from SK-N-MC neuroblastoma cells were found to harbor substantial histone deacetylase activity, which was likely conferred by the nucleosome remodeling and deacetylation (NuRD) complex. CTIP2 was found to associate with the NuRD complex through direct interaction with both RbAp46 and RbAp48, and components of the NuRD complex were found to be recruited to an artificial promoter template in a CTIP2-dependent manner in transfected cells. Finally, the NuRD complex and CTIP2 were found to co-occupy the promoter template of p57KIP2, a gene encoding a cyclin-dependent kinase inhibitor, and identified herein as a novel transcriptional target of CTIP2 in SK-N-MC cells. Therefore, it seems likely that the NuRD complex may be involved in transcriptional repression of CTIP2 target genes and contribute to the function(s) of CTIP2 within a neuronal context.

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