The mouse C/EBPδ gene promoter is regulated by STAT3 and Sp1 transcriptional activators, chromatin remodeling and c-Myc repression

2007 ◽  
Vol 102 (5) ◽  
pp. 1256-1270 ◽  
Author(s):  
Yingjie Zhang ◽  
Said Sif ◽  
Jim DeWille
1987 ◽  
Vol 7 (3) ◽  
pp. 1129-1138
Author(s):  
W D Morgan ◽  
G T Williams ◽  
R I Morimoto ◽  
J Greene ◽  
R E Kingston ◽  
...  

We characterized the activity of a human hsp70 gene promoter by in vitro transcription. Analysis of 5' deletion and substitution mutants in HeLa nuclear extracts showed that the basal activity of the promoter depends primarily on a CCAAT-box sequence located at -65. A protein factor, CCAAT-box-binding transcription factor (CTF), was isolated from HeLa nuclear extracts and shown to be responsible for stimulation of transcription in a reconstituted in vitro system. DNase I footprinting revealed that CTF interacts with two CCAAT-box elements located at -65 and -147 of the human hsp70 promoter. An additional binding activity, heat shock transcription factor (HSTF), which interacted with the heat shock element, was also identified in HeLa extract fractions. This demonstrates that the promoter of this human hsp70 gene interacts with at least two positive transcriptional activators, CTF, which is required for CCAAT-box-dependent transcription as in other promoters such as those of globin and herpes simplex virus thymidine kinase genes, and HSTF, which is involved in heat inducibility.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1456
Author(s):  
Angela Minervini ◽  
Nicoletta Coccaro ◽  
Luisa Anelli ◽  
Antonella Zagaria ◽  
Giorgina Specchia ◽  
...  

The high mobility group AT-Hook (HMGA) proteins are a family of nonhistone chromatin remodeling proteins known as “architectural transcriptional factors”. By binding the minor groove of AT-rich DNA sequences, they interact with the transcription apparatus, altering the chromatin modeling and regulating gene expression by either enhancing or suppressing the binding of the more usual transcriptional activators and repressors, although they do not themselves have any transcriptional activity. Their involvement in both benign and malignant neoplasias is well-known and supported by a large volume of studies. In this review, we focus on the role of the HMGA proteins in hematological malignancies, exploring the mechanisms through which they enhance neoplastic transformation and how this knowledge could be exploited to devise tailored therapeutic strategies.


2014 ◽  
Vol 35 (5) ◽  
pp. 847-855 ◽  
Author(s):  
Ryuta Asada ◽  
Naomichi Takemata ◽  
Charles S. Hoffman ◽  
Kunihiro Ohta ◽  
Kouji Hirota

The Tup family corepressors contribute to critical cellular responses, such as the stress response and differentiation, presumably by inducing repressive chromatin, though the precise repression mechanism remains to be elucidated. TheSchizosaccharomyces pombefission yeast Tup family corepressors Tup11 and Tup12 (Tup11/12), which are orthologs of Tup1 inSaccharomyces cerevisiaebudding yeast and Groucho inDrosophila, negatively control chromatin and the transcriptional activity of some stress-responsive genes. Here, we demonstrate that Tup11/12 repress transcription of a gluconeogenesis gene,fbp1+, by three distinct mechanisms. First, Tup11/12 inhibit chromatin remodeling in thefbp1+promoter region where the Atf1 and Rst2 transcriptional activators bind. Second, they repress the formation of an open chromatin configuration at thefbp1+TATA box. Third, they repress mRNA transcriptionper seby regulating basic transcription factors. These inhibitory actions of Tup11/12 are antagonized by three different types of transcriptional activators: CREB/ATF-type Atf1, C2H2zinc finger-type Rst2, and CBF/NF-Y-type Php5 proteins. We also found that impaired chromatin remodeling andfbp1+mRNA transcription inphp5Δ strains are rescued by the double deletions oftup11+andtup12+, although the distribution of the transcription start sites becomes broader than that in wild-type cells. These data reveal a new mechanism of precise determination of the mRNA start site by Tup family corepressors and CBF/NF-Y proteins.


2007 ◽  
Vol 282 (13) ◽  
pp. 9445-9457 ◽  
Author(s):  
José Gutiérrez ◽  
Roberto Paredes ◽  
Fernando Cruzat ◽  
David A. Hill ◽  
Andre J. van Wijnen ◽  
...  

2007 ◽  
Vol 85 (4) ◽  
pp. 419-425 ◽  
Author(s):  
Martin Montecino ◽  
Janet L. Stein ◽  
Gary S. Stein ◽  
Jane B. Lian ◽  
Andre J. van Wijnen ◽  
...  

Chromatin organization within the nuclear compartment is a fundamental mechanism to regulate the expression of eukaryotic genes. During the last decade, a number of nuclear protein complexes with the ability to remodel chromatin and regulate gene transcription have been reported. Among these complexes is the SWI/SNF family, which alters chromatin structure in an ATP-dependent manner. A considerable effort has been made to understand the molecular mechanisms by which SWI/SNF catalyzes nucleosome remodeling. However, limited attention has been dedicated to studying the role of the DNA sequence in this remodeling process. Therefore, in this minireview, we discuss the contribution of nucleosome positioning and nucleosome excluding sequences to the targeting and activity of SWI/SNF complexes. This discussion includes results from our group using the rat osteocalcin gene promoter as a model. Based on these results, we postulate a model for chromatin remodeling and transcriptional activation of this gene in osteoblastic cells.


Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 711-720 ◽  
Author(s):  
Tipayaratn Musikacharoen ◽  
Asako Oguma ◽  
Yasunobu Yoshikai ◽  
Norika Chiba ◽  
Akio Masuda ◽  
...  

AbstractInterleukin-12 receptor β1 (IL12RB1) is expressed on a variety of immune cells, including T and natural killer (NK) cells and macrophages, and is involved in innate and adaptive immune responses. Levels of IL12RB1 mRNA are dynamically regulated by various cytokines, including interferon-γ (IFN-γ) and IL-15. To reveal the regulatory mechanisms governing IL12RB1 gene expression, we analyzed the transcriptional regulatory region of the mouse IL12RB1 gene. Promoter analyses in a mouse macrophage cell line, RAW264.7, revealed that the 2508-bp region upstream of the transcriptional start site is sufficient for the full transcriptional activation of the IL12RB1 gene by IFN-γ or IL-15. Analyses of the deletion mutants revealed critical roles of IRE/ISRE and ETS/PU.1 elements, to which IRF3 and PU.1, respectively, bound. Notably, chromatin immunoprecipitation (ChIP) assays revealed IL-15 rapidly induced histone H3 acetylation at the IL12RB1 promoter. Consistently, IL-15, as a histone deacetylase inhibitor, synergistically enhanced IL12RB1 gene expression and promoter activation by IFN-γ through increased protein binding to ETS/PU.1 and IRE/ISRE sites. Additionally, IL12RB1 promoter activation by IFN-γ was enhanced by the coexpression of a coactivator protein, CBP. Thus, IL-15 induces chromatin remodeling of the IL12RB1 gene promoter, increasing IL12RB1 mRNA expression in synergy with IFN-γ through the recruitment of PU.1 and IRF3.


Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2465
Author(s):  
Maciej Sobczak ◽  
Magdalena Strachowska ◽  
Karolina Gronkowska ◽  
Iwona Karwaciak ◽  
Łukasz Pułaski ◽  
...  

The increased level of hydrogen peroxide accompanies some modes of macrophage specification and is linked to ROS-based antimicrobial activity of these phagocytes. In this study, we show that activation of toll-like receptors with bacterial components such as LPS is accompanied by the decline in transcription of hydrogen peroxide decomposing enzyme-catalase, suppression of which facilitates the polarization of human macrophages towards the pro-inflammatory phenotype. The chromatin remodeling at the CAT promoter involves LSD1 and HDAC1, but activity of the first enzyme defines abundance of the two proteins on chromatin, histone acetylation status and the CAT transcription. LSD1 inhibition prior to macrophage activation with LPS prevents CAT repression by enhancing the LSD1 and interfering with the HDAC1 recruitment to the gene promoter. The maintenance of catalase level with LSD1 inhibitors during M1 polarization considerably limits LPS-triggered expression of some pro-inflammatory cytokines and markers such as IL1β, TNFα, COX2, CD14, TLR2, and IFNAR, but the effect of LSD1 inhibitors is lost upon catalase deficiency. Summarizing, activity of LSD1 allows for the CAT repression in LPS stimulated macrophages, which negatively controls expression of some key pro-inflammatory markers. LSD1 inhibitors can be considered as possible immunosuppressive drugs capable of limiting macrophage M1 specialization.


1995 ◽  
Vol 23 (7) ◽  
pp. 1119-1126 ◽  
Author(s):  
Ron P. H. Dirks ◽  
Hans J. Jansen ◽  
Bart van Gerven ◽  
Carla Onnekink ◽  
Henri P. J. Bloemers

1987 ◽  
Vol 7 (3) ◽  
pp. 1129-1138 ◽  
Author(s):  
W D Morgan ◽  
G T Williams ◽  
R I Morimoto ◽  
J Greene ◽  
R E Kingston ◽  
...  

We characterized the activity of a human hsp70 gene promoter by in vitro transcription. Analysis of 5' deletion and substitution mutants in HeLa nuclear extracts showed that the basal activity of the promoter depends primarily on a CCAAT-box sequence located at -65. A protein factor, CCAAT-box-binding transcription factor (CTF), was isolated from HeLa nuclear extracts and shown to be responsible for stimulation of transcription in a reconstituted in vitro system. DNase I footprinting revealed that CTF interacts with two CCAAT-box elements located at -65 and -147 of the human hsp70 promoter. An additional binding activity, heat shock transcription factor (HSTF), which interacted with the heat shock element, was also identified in HeLa extract fractions. This demonstrates that the promoter of this human hsp70 gene interacts with at least two positive transcriptional activators, CTF, which is required for CCAAT-box-dependent transcription as in other promoters such as those of globin and herpes simplex virus thymidine kinase genes, and HSTF, which is involved in heat inducibility.


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