Investigating actinomycin D binding to G-quadruplex, i-motif and double-stranded DNA in 27-nt segment of c-MYC gene promoter

2016 ◽  
Vol 58 ◽  
pp. 1188-1193 ◽  
Author(s):  
Zhila Niknezhad ◽  
Leila Hassani ◽  
Davood Norouzi
Keyword(s):  
Actinomycin D ◽  
Gene Promoter ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
Myc Gene

scholarly journals Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3692-3700 ◽  
Author(s):  
Hui-Ping Gu ◽  
Sen Lin ◽  
Ming Xu ◽  
Hai-Yi Yu ◽  
Xiao-Jun Du ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Gene Promoter ◽  
Binding Motif ◽  
Endogenous Expression ◽  
G Quadruplex

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.

c-myc RNA degradation in growing and differentiating cells: possible alternate pathways

1989 ◽  
Vol 9 (1) ◽  
pp. 288-295
Author(s):  
S G Swartwout ◽  
A J Kinniburgh
Keyword(s):  
Actinomycin D ◽  
Rna Degradation ◽  
Transcriptional Elongation ◽  
Rna Turnover ◽  
Rapid Degradation ◽  
Polyadenylated Rna ◽  
Myc Gene ◽  
Fail Safe ◽  
Kinetics Of ◽  
In Cells

Transcripts of the proto-oncogene c-myc are composed of a rapidly degraded polyadenylated RNA species and an apparently much more stable, nonadenylated RNA species. In this report, the extended kinetics of c-myc RNA turnover have been examined in rapidly growing cells and in cells induced to differentiate. When transcription was blocked with actinomycin D in rapidly growing cells, poly(A)+ c-myc was rapidly degraded (t1/2 = 12 min). c-myc RNA lacking poly(A) initially remained at or near control levels; however, after 80 to 90 min it was degraded with kinetics similar to those of poly(A)+ c-myc RNA. These bizarre kinetics are due to the deadenylation of poly(A)+ c-myc RNA to form poly(A)- c-myc, thereby initially maintaining the poly(A)- c-myc RNA pool when transcription is blocked. In contrast to growing cells, cells induced to differentiate degraded both poly(A)+ and poly(A)- c-myc RNA rapidly. The rapid disappearance of both RNA species in differentiating cells suggests that a large proportion of the poly(A)+ c-myc RNA was directly degraded without first being converted to poly(A)- c-myc RNA. Others have shown that transcriptional elongation of the c-myc gene is rapidly blocked in differentiating cells. We therefore hypothesize that in differentiating cells a direct, rapid degradation of poly(A)+ c-myc RNA may act as a backup or fail-safe system to ensure that c-myc protein is not synthesized. This tandem system of c-myc turnoff may also make cells more refractory to mutations which activate constitutive c-myc expression.

Thiazole Orange-Modified Carbon Dots for Ratiometric Fluorescence Detection of G-Quadruplex and Double-Stranded DNA

2018 ◽  
Vol 10 (30) ◽  
pp. 25166-25173 ◽  
Author(s):  
Ming Jin ◽  
Xiangjun Liu ◽  
Xin Zhang ◽  
Linlin Wang ◽  
Tao Bing ◽  
...  
Keyword(s):  
Fluorescence Detection ◽  
Carbon Dots ◽  
Thiazole Orange ◽  
Ratiometric Fluorescence ◽  
Double Stranded Dna ◽  
G Quadruplex

CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms

1993 ◽  
Vol 13 (12) ◽  
pp. 7612-7624
Author(s):  
E M Klenova ◽  
R H Nicolas ◽  
H F Paterson ◽  
A F Carne ◽  
C M Heath ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Lines ◽  
Gene Promoter ◽  
Differentially Expressed ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Mobility Shift ◽  
Chicken Cell ◽  
Nuclear Extracts ◽  
Myc Gene

A novel sequence-specific DNA-binding protein, CTCF, which interacts with the chicken c-myc gene promoter, has been identified and partially characterized (V. V. Lobanenkov, R. H. Nicolas, V. V. Adler, H. Paterson, E. M. Klenova, A. V. Polotskaja, and G. H. Goodwin, Oncogene 5:1743-1753, 1990). In order to test directly whether binding of CTCF to one specific DNA region of the c-myc promoter is important for chicken c-myc transcription, we have determined which nucleotides within this GC-rich region are responsible for recognition of overlapping sites by CTCF and Sp1-like proteins. Using missing-contact analysis of all four nucleotides in both DNA strands and homogeneous CTCF protein purified by sequence-specific chromatography, we have identified three sets of nucleotides which contact either CTCF or two Sp1-like proteins binding within the same DNA region. Specific mutations of 3 of 15 purines required for CTCF binding were designed to eliminate binding of CTCF without altering the binding of other proteins. Electrophoretic mobility shift assay of nuclear extracts showed that the mutant DNA sequence did not bind CTCF but did bind two Sp1-like proteins. When introduced into a 3.3-kbp-long 5'-flanking noncoding c-myc sequence fused to a reporter CAT gene, the same mutation of the CTCF binding site resulted in 10- and 3-fold reductions, respectively, of transcription in two different (erythroid and myeloid) stably transfected chicken cell lines. Isolation and analysis of the CTCF cDNA encoding an 82-kDa form of CTCF protein shows that DNA-binding domain of CTCF is composed of 11 Zn fingers: 10 are of C2H2 class, and 1 is of C2HC class. CTCF was found to be abundant and conserved in cells of vertebrate species. We detected six major nuclear forms of CTCF protein differentially expressed in different chicken cell lines and tissues. We conclude that isoforms of 11-Zn-finger factor CTCF which are present in chicken hematopoietic HD3 and BM2 cells can act as a positive regulator of the chicken c-myc gene transcription. Possible functions of other CTCF forms are discussed.

scholarly journals Chasing Particularities of Guanine- and Cytosine-Rich DNA Strands

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 434 ◽  
Author(s):  
Marko Trajkovski ◽  
Janez Plavec
Keyword(s):  
Structural Changes ◽  
Polyacrylamide Gel Electrophoresis ◽  
Dna Recombination ◽  
Cd Spectroscopy ◽  
G Quadruplex ◽  
Recombination Processes ◽  
Dna Strands ◽  
Native Polyacrylamide Gel Electrophoresis ◽  
Myc Gene

By substitution of natural nucleotides by their abasic analogs (i.e., 1′,2′-dideoxyribose phosphate residue) at critically chosen positions within 27-bp DNA constructs originating from the first intron of N-myc gene, we hindered hybridization within the guanine- and cytosine-rich central region and followed formation of non-canonical structures. The impeded hybridization between the complementary strands leads to time-dependent structural transformations of guanine-rich strand that are herein characterized with the use of solution-state NMR, CD spectroscopy, and native polyacrylamide gel electrophoresis. Moreover, the DNA structural changes involve transformation of intra- into inter-molecular G-quadruplex structures that are thermodynamically favored. Intriguingly, the transition occurs in the presence of complementary cytosine-rich strands highlighting the inability of Watson–Crick base-pairing to preclude the transformation between G-quadruplex structures that occurs via intertwining mechanism and corroborates a role of G-quadruplex structures in DNA recombination processes.

scholarly journals Selective recognition of human telomeric G-quadruplex with designed peptide via hydrogen bonding followed by base stacking interactions

RSC Advances ◽  
2019 ◽  
Vol 9 (69) ◽  
pp. 40255-40262 ◽  
Author(s):  
Shikhar Tyagi ◽  
Sarika Saxena ◽  
Nikita Kundu ◽  
Taniya Sharma ◽  
Amlan Chakraborty ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Synthetic Peptide ◽  
High Selectivity ◽  
Selective Recognition ◽  
Stacking Interactions ◽  
Base Stacking ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
Guanine Base

A new synthetic peptide is presented. A Glu residue binds through H-bonding to a guanine-base and a Trp residue intercalates with K+ resulting in stabilization of a human telomeric G-quadruplex with high selectivity over a complementary c-rich strand and double-stranded DNA.

G-Quadruplex-Specific Cell-Permeable Guanosine–Anthracene Conjugate Inhibits Telomere Elongation and Induces Apoptosis by Repressing the c-MYC Gene

2019 ◽  
Vol 30 (12) ◽  
pp. 3038-3045 ◽  
Author(s):  
Puja Saha ◽  
Y. Pavan Kumar ◽  
Tania Das ◽  
Diana Müller ◽  
Irene Bessi ◽  
...  
Keyword(s):  
Specific Cell ◽  
Telomere Elongation ◽  
G Quadruplex ◽  
Myc Gene
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