scholarly journals Molecular Study of Cellulase Gene Transcription Regulatory Elements via EMS Mutagenesis in a Novelthermophilic Cellulytic Bacillus sp.

2017 ◽  
Vol 6 (12) ◽  
pp. 1664-1670
Keyword(s):  
Gene Transcription ◽  
Molecular Study ◽  
Regulatory Elements ◽  
Bacillus Sp ◽  
Cellulase Gene ◽  
Ems Mutagenesis

Protein signaling and regulation of gene transcription in leukemia: role of the Casein Kinase II-Ikaros axis

2016 ◽  
Vol 64 (3) ◽  
pp. 735-739 ◽  
Author(s):  
Chandrika S Gowda ◽  
Chunhua Song ◽  
Yali Ding ◽  
Malika Kapadia ◽  
Sinisa Dovat
Keyword(s):  
Gene Transcription ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Lymphoblastic Leukemia ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Casein Kinase Ii ◽  
Casein Kinase ◽  
Protein Signaling

Protein signaling and regulation of gene expression are the two major mechanisms that regulate cellular proliferation in leukemia. Discerning the function of these processes is essential for understanding the pathogenesis of leukemia and for developing the targeted therapies. Here, we provide an overview of one of the mechanisms that regulates gene transcription in leukemia. This mechanism involves the direct interaction between Casein Kinase II (CK2) and the Ikaros transcription factor. Ikaros (IKZF1) functions as a master regulator of hematopoiesis and a tumor suppressor in acute lymphoblastic leukemia (ALL). Impaired Ikaros function results in the development of high-risk leukemia. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. In vivo, Ikaros is a target for CK2, a pro-oncogenic kinase. CK2 directly phosphorylates Ikaros at multiple amino acids. Functional experiments showed that CK2-mediated phosphorylation of Ikaros, regulates Ikaros’ DNA binding affinity, subcellular localization and protein stability. Recent studies revealed that phosphorylation of Ikaros by CK2 regulates Ikaros binding and repression of the terminal deoxytransferase (TdT) gene in normal thymocytes and in T-cell ALL. Available data suggest that the oncogenic activity of CK2 in leukemia involves functional inactivation of Ikaros and provide a rationale for CK2 inhibitors as a potential treatment for ALL.

scholarly journals Transcription factor MBF-I interacts with metal regulatory elements of higher eucaryotic metallothionein genes.

1989 ◽  
Vol 9 (12) ◽  
pp. 5315-5323 ◽  
Author(s):  
J Imbert ◽  
M Zafarullah ◽  
V C Culotta ◽  
L Gedamu ◽  
D Hamer
Keyword(s):  
Gene Transcription ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Direct Role ◽  
Transcription In Vitro ◽  
Mouse Cells ◽  
Affinity Reagent

Metallothionein (MT) gene promoters in higher eucaryotes contain multiple metal regulatory elements (MREs) that are responsible for the metal induction of MT gene transcription. We identified and purified to near homogeneity a 74-kilodalton mouse nuclear protein that specifically binds to certain MRE sequences. This protein, MBF-I, was purified employing as an affinity reagent a trout MRE that is shown to be functional in mouse cells but which lacks the G+C-rich and SP1-like sequences found in many mammalian MT gene promoters. Using point-mutated MREs, we showed that there is a strong correlation between DNA binding in vitro and MT gene regulation in vivo, suggesting a direct role of MBF-I in MT gene transcription. We also showed that MBF-I can induce MT gene transcription in vitro in a mouse extract and that this stimulation requires zinc.

scholarly journals A proximal tissue-specific module and a distal negative regulatory module control apolipoprotein(a) gene transcription

2004 ◽  
Vol 379 (1) ◽  
pp. 151-159 ◽  
Author(s):  
Sarita NEGI ◽  
Saurabh K. SINGH ◽  
Nirupma PATI ◽  
Vikas HANDA ◽  
Ruchi CHAUHAN ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Hela Cells ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Tissue Specific ◽  
Apolipoprotein A ◽  
Regulatory Module ◽  
Specific Manner

The apo(a) [apolipoprotein(a)] gene is responsible for variations in plasma lipoprotein(a), high levels of which are a risk factor for atherosclerosis and myocardial infarction. The apo(a) promoter stimulates the expression of reporter genes in HepG2 cells, but not in HeLa cells. In the present study, we demonstrate that the 1.4 kb apo(a) promoter comprises two composite regulatory regions: a distal negative regulatory module (positions −1432 to −716) and a proximal tissue-specific module (−716 to −616). The distal negative regulatory module contains two strong negative regulatory regions [polymorphic PNR (pentanucleotide repeat region) and NREβ (negative regulatory element β)], which sandwich the postive regulatory region PREβ (positive regulatory element β). The PNR was shown to bind to transcription factors in a tissue-specific manner, whereas the ubiquitous transcription factors hepatocyte nuclear factor 3α and GATA binding protein 4 bound to NREβ to repress gene transcription. The proximal tissue-specific module contains two regulatory elements: an activating region (PREα) that activates transcription in HepG2 cells, and NREα, which is responsible for repressing the apo(a) gene in HeLa cells. NREα binds to a HeLa-specific repressor. These multiple regulatory elements might work co-operatively to finely regulate apo(a) gene expression. Although the tissue-specific module is required for apo(a) gene activation and repression in a tissue-specific manner, the combinatorial interplay of the distal and proximal regulators might define the complex pathway(s) of apo(a) gene regulation.

scholarly journals Functional Cooperation between Multiple Regulatory Elements in the Untranslated Exon 1 Stimulates the Basal Transcription of the Human GnRH-II Gene

2003 ◽  
Vol 17 (7) ◽  
pp. 1175-1191 ◽  
Author(s):  
Chi Keung Cheng ◽  
Ruby L. C. Hoo ◽  
Billy K. C. Chow ◽  
Peter C. K. Leung
Keyword(s):  
Gene Transcription ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Mutational Analysis ◽  
Regulatory Elements ◽  
Start Codon ◽  
Basal Transcription ◽  
Untranslated Exon ◽  
E Box ◽  
Exon 1

Abstract The wide distribution of GnRH-II and conservation of its structure over all vertebrate classes suggest that the neuropeptide possesses vital biological functions. Although recent studies have shown that the expression of the human GnRH-II gene is regulated by cAMP and estrogen, the molecular mechanisms governing its basal transcription remain poorly understood. Using the neuronal TE-671 and placental JEG-3 cells, we showed that the minimal human GnRH-II promoter was located between nucleotide −1124 and −750 (relative to the translation start codon) and that the untranslated exon 1 was important to produce full promoter activity. Two putative E-box binding sites and one Ets-like element were identified within the first exon, and mutational analysis demonstrated that these cis-acting elements functioned cooperatively to stimulate the human GnRH-II gene transcription. EMSAs, UV cross-linking, and Southwestern blot analyses indicated that the basic helix-loop-helix transcription factor AP-4 bound specifically to the two E-box binding sites, whereas an unidentified protein bound to the Ets-like element. The functional importance of AP-4 in controlling human GnRH-II gene transcription was demonstrated by overexpression of sense and antisense full-length AP-4 cDNAs. Taken together, our present data demonstrate a novel mechanism in stimulating basal human GnRH-II gene transcription mediated by cooperative actions of multiple regulatory elements within the untranslated first exon of the gene.

scholarly journals A Novel Regulatory Protein Involved in Motility of Vibrio cholerae

2009 ◽  
Vol 191 (22) ◽  
pp. 7027-7038 ◽  
Author(s):  
Manuel Moisi ◽  
Christian Jenul ◽  
Susan M. Butler ◽  
Aaron New ◽  
Sarah Tutz ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Gene Transcription ◽  
Deletion Mutant ◽  
Expression Patterns ◽  
Regulatory Protein ◽  
Regulatory Elements ◽  
Flagellar Gene ◽  
Class Iii ◽  
Reading Frame ◽  
Infant Mouse

ABSTRACT The facultative pathogen Vibrio cholerae is the causative agent of the human intestinal disease cholera. Both motility and chemotaxis of V. cholerae have been shown to contribute to the virulence and spread of cholera. The flagellar gene operons are organized into a hierarchy composed of four classes (I to IV) based on their temporal expression patterns. Some regulatory elements involved in flagellar gene expression have been elucidated, but regulation is complex and flagellar biogenesis in V. cholerae is not completely understood. In this study, we determined that the virulence defect of a V. cholerae cheW1 deletion mutant was due to polar effects on the downstream open reading frame VC2058 (flrD). Expression of flrD in trans restored the virulence defect of the cheW1 deletion mutant, and deletion of flrD resulted in a V. cholerae strain attenuated for virulence, as determined by using the infant mouse intestinal colonization model. The flrD mutant strain exhibited decreased transcription of class III and IV flagellar genes and reduced motility. Transcription of the flrD promoter, which lies within the coding sequence of cheW1, is independent of the flagellar transcriptional activators FlrA and RpoN, which activate class II genes, indicating that flrD does not fit into any of the four flagellar gene classes. Genetic epistasis studies revealed that the two-component system FlrBC, which is required for class III and IV flagellar gene transcription, acts downstream of flrD. We hypothesize that the inner membrane protein FlrD interacts with the cytoplasmic FlrBC complex to activate class III and IV gene transcription.

scholarly journals Transcription of the interleukin 4 gene is regulated by multiple promoter elements.

1993 ◽  
Vol 177 (6) ◽  
pp. 1663-1674 ◽  
Author(s):  
M D Todd ◽  
M J Grusby ◽  
J A Lederer ◽  
E Lacy ◽  
A H Lichtman ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Dna Sequences ◽  
Interleukin 2 ◽  
Regulatory Elements ◽  
Inducible Expression ◽  
Interleukin 4 ◽  
Upstream Sequence ◽  
Tissue Specific ◽  
Cytokine Genes

Activation of T helper cell 1 (Th1) and Th2 results in transcription of the interleukin 2 (IL-2) and IL-4 cytokine genes, respectively. Whereas many of the regulatory elements and factors responsible for IL-2 transcription in T cells are well defined, little is known about parallel mechanisms that drive transcription of the IL-4 gene. Here we have analyzed the murine IL-4 promoter, both in vivo and in a Th2 clone. 3 kb of IL-4 upstream sequence is shown to be sufficient to achieve tissue-specific and inducible expression of a thymidine kinase reporter gene in vivo in a manner that mirrors the expression of endogenous IL-4. Tissue-specific and inducible expression is also demonstrated in a Th2 clone, but not in a B cell line. Deletional and mutational analysis of the IL-4 promoter demonstrated that sequences from -100 to -28 were necessary for a transcriptional response to Concanavalin A or anti-CD3 monoclonal antibody. An overlapping, yet smaller region, spanning the sequences from -60 to -28 bp was shown to be required for the response to ionomycin. Mutation of an 8-bp region from -43 to -35 of the IL-4 promoter completely abrogated IL-4 gene transcription in response to all stimuli tested. In addition, our results show that the effects of the immunosuppressive agent Cyclosporin A map to the same DNA sequences as the positive control elements. These results identify DNA sequences that are functionally important for the control of IL-4 gene transcription both in vivo and in vitro. Although these sequences are highly conserved in the human and murine IL-4 genes, they are largely not present in the IL-2 enhancer complex. Thus, cytokine-specific cis-acting elements may be one mechanism by which these two cytokine genes are differentially regulated.

scholarly journals O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1666
Author(s):  
Matthew Parker ◽  
Kenneth Peterson ◽  
Chad Slawson
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Gene Transcription ◽  
Regulatory Elements ◽  
Post Translational Modification ◽  
Hexosamine Biosynthetic Pathway ◽  
Rnap Ii ◽  
Tata Box Binding Protein

O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar post-translational modification (PTM) of intracellular proteins linking nutrient flux through the Hexosamine Biosynthetic Pathway (HBP) to the control of cis-regulatory elements in the genome. Aberrant O-GlcNAcylation is associated with the development, progression, and alterations in gene expression in cancer. O-GlcNAc cycling is defined as the addition and subsequent removal of the modification by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) provides a novel method for cells to regulate various aspects of gene expression, including RNA polymerase function, epigenetic dynamics, and transcription factor activity. We will focus on the complex relationship between phosphorylation and O-GlcNAcylation in the regulation of the RNA Polymerase II (RNAP II) pre-initiation complex and the regulation of the carboxyl-terminal domain of RNAP II via the synchronous actions of OGT, OGA, and kinases. Additionally, we discuss how O-GlcNAcylation of TATA-box binding protein (TBP) alters cellular metabolism. Next, in a non-exhaustive manner, we will discuss the current literature on how O-GlcNAcylation drives gene transcription in cancer through changes in transcription factor or chromatin remodeling complex functions. We conclude with a discussion of the challenges associated with studying O-GlcNAcylation and present several new approaches for studying O-GlcNAc regulated transcription that will advance our understanding of the role of O-GlcNAc in cancer.

scholarly journals COMPUTATIONAL IDENTIFICATION OF PROMOTER REGIONS IN PROKARYOTES AND EUKARYOTES

2021 ◽  
pp. 21-28
Author(s):  
Sudheer Menon ◽  
Shanmughavel Piramanayakam ◽  
Gopal Agarwal
Keyword(s):  
Gene Transcription ◽  
Transcription Initiation ◽  
Computational Models ◽  
Score Function ◽  
Regulatory Elements ◽  
Promoter Regions ◽  
Precise Calculation ◽  
Distinguishing Sequences ◽  
Regulatory Dna

Promoters are modular DNA structures that contain complex regulatory elements required for the initiation of gene transcription. Therefore, the use of machine learning methods to identify promoters is very important for improving genome annotation and understanding transcriptional regulation. In recent years, many methods for predicting eukaryotic and prokaryotic promoters have been proposed. However, the performance of these methods is still far from satisfactory. In this article, we have developed a hybrid method (called IPMD) that combines a position correlation score function and diversity increment with modified Mahalanobis Discriminant to predict eukaryotic and prokaryotic promoters. The precise calculation and identification of promoters remains a challenge because these key DNA regulatory regions have variable structures composed of functional motifs that can provide gene-specific transcription initiation. The promoter is a regulatory DNA region, which is very important for gene transcription regulation. It is located near the transcription start site (TSS) upstream of the corresponding gene. In the post-genomics era, the availability of data makes it possible to build computational models to detect promoters robustly, because these models are expected to be helpful to academia and drug discovery. Until recently, the developed model only focused on distinguishing sequences into promoters and non-promoters. However, by considering the classification of weak and strong promoters, promoter predictors can be further improved. INDEX TERMS—: deep learning, DNA sequence analysis, Promoter prediction, Promoters, Promoter elements

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